Research ArticleFormulation of Suppositories of Alum Produced from BauxiteWaste in Ghana for the Treatment of Hemorrhoid

Daniel A Bartels1 Raphael Johnson 1 Marcel T Bayor1 George K Ainooson2

Paul P S Ossei3 Rashid K Etuaful4 and Richard Buamah4

1Department of Pharmaceutics College of Health Sciences Kwame Nkrumah University of Scienceand Technology Kumasi Ghana2Department of Pharmacology College of Health Sciences Kwame Nkrumah University of Scienceand Technology Kumasi Ghana3Department of Pathology College of Health Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana4Department of Civil Engineering College of Engineering Kwame Nkrumah University ofScience and Technology Kumasi Ghana

Correspondence should be addressed to Raphael Johnson rjohnsonpharmknustedugh

Received 2 December 2020 Accepted 4 May 2021 Published 13 May 2021

Academic Editor Isabel Del Hierro

Copyright copy 2021 Daniel A Bartels et al )is is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

)e study sought to formulate and evaluate suppositories using a locally produced brand of alum (Aw) obtained from bauxitewaste generated at Awaso bauxite mine in the Western-North region of Ghana for use in the treatment of hemorrhoids )esuppositories were formulated using shea butter modified respectively with amounts of beeswax and theobroma oil In anotherdevelopment theobroma oil was modified with different concentrations of beeswax Drug-base interactions were investigatedusing attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy)e suppositories were prepared using thehot melt and triturationmethods Quality control checks were carried out on the formulations)e evaluated parameters includedphysical characteristics (texture presence or absence of entrapped air and contraction holes) weight uniformity disintegrationtime drug content and in vitro release profile of the alum from the formulated suppositories An in vivo analysis was carried outon the most suitable formulation to ascertain its efficacy on inflamed tissues using croton oil-induced rectal inflammation in a ratmodel A critical examination of the ATR-FTIR spectra revealed no drug-base interactions )e suppository formulations passedall Pharmacopoeia stated tests )e in vivo study revealed the use of suppositories ameliorated the croton oil-induced hemorrhoidin the rectoanal region of the rats

1 Introduction

Hemorrhoids also called piles are swollen veins in the anusand lower rectum similar to varicose veins Hemorrhoids candevelop inside the rectum (internal hemorrhoids) or underthe skin around the anus (external hemorrhoids) It occursfrequently as an inflammatory process of the hemorrhoidalplexus [1] )ey are often not associated with any symptomsand people may not know they have them When symptomsdo occur they present as bleeding andor pain on passingstool sense of incomplete bowel emptying a lump around orinside the anus itchiness or soreness around the anus and

mucus discharge from the anus [2] Hemorrhoids affect about44 of the general population worldwide irrespective ofgender However it is more frequent in females than in maleswith age between 45 and 65 years Caucasians are affectedmore frequently than African Americans and higher socio-economic status is associated with increased prevalence [3]Long-term constipation diarrhoea long duration of sittingstrenuous manual performance involving lifting agingobesity overuse of laxatives and pregnancy are consideredsome of the risk factors that could lead to the development ofhemorrhoids [2 4] Despite its low morbidity hemorrhoidshave a high impact on quality of life

Hindawie Scientific World JournalVolume 2021 Article ID 6667562 13 pageshttpsdoiorg10115520216667562

Management of symptomatic hemorrhoids ranges fromnonoperative medical interventions (drugs dietary andlifestyle modification) and office-based procedures (rubberband ligation sclerotherapy and infrared coagulation) tosurgery (hemorrhoidectomy stapled hemorrhoidopexy andDoppler-guided haemorrhoid artery ligation) [2] Lifestylemodification includes increasing oral fluid intake reducingfat consumption avoiding straining and regular exerciseIncreasing the intake of fibre-rich diet is recommended [5]Pharmacological treatment of haemorrhoid aims at reducinginflammation pain and bleeding Topical dosage forms suchas creams ointments and suppositories containing steroids(corticosteroids) or nonsteroidal anti-inflammatory agents(NSAIDS ibuprofen aspirin and diclofenac) either aloneor in combination with antibiotics or anaesthetics (such aslidocaine benzocaine and dibucaine) have been shown tobe effective However their prolonged use is limited due tothe high incidence of side effects [6ndash8] Creams and oint-ments are commonly applied to external hemorrhoids fortemporary relief Rectal suppositories are better for internalhemorrhoids Suppositories are usually inserted after abowel movement so the effect can last longer because theybreak down more slowly releasing medication over a longerperiod of time )e medicine is absorbed by the rectal tissueand can help all discomfort and pain caused by hemorrhoidsSuppositories are prepared using bases as vehicles )e basesare of two types oleagineousfatty bases (theobroma oil orcocoa butter and hydrogenated vegetable oils) and watermiscible or soluble (glycerinated gelatin and polyethyleneglycol polymers also known as macrogols) )e type of baseused depends on the physicochemical properties of the drugto be incorporated [9 10] Commercially available fattybases which are considered as cocoa butter substitutes in-clude Dehydagreg Hydrokotereg Suppocirereg and WitepsolregHydrocortisone and NSAID-containing suppositories suchas Anusol-HCreg Anucort-HCreg Voltarolreg and Voltareneregare formulated using hydrogenated vegetable oils [9 11])ese bases are very stable to oxidation have a longer shelf-life set quickly and do not exhibit polymorphism )ey arehowever costly and have to be imported for use

Alum is a double salt of sulphate bonded to potassiumand aluminium coordinated to molecules of water[KAl(SO4)2middot12middotH2O] Alum can be obtained from mineralssuch as kalinite alunite leucite and bauxite [12] It is mostlyknown for its use in the purification of water [13] Howeveralum has other uses such as making paper fireproof textilesand deodorants [14] In recent years scientific studies haveproven that alum has pharmacological properties such asantihemorrhagic antimicrobial and anti-inflammatory [15]Nonsteroidal anti-inflammatory drugs are more tolerable tomost people than corticosteroids )e anti-inflammatoryand antihemorrhagic effects could make alum a useful activeingredient in the treatment of hemorrhoids Alum iscommercially produced by a hydrometallurgical process)is process begins with extraction of alumina (solid Al2O3)from bauxite waste with the help of an aqueous solution ofsulphuric acid )e resultant solution is then reacted withpotassium sulphate to produce potassium aluminium sul-phate [16] In Ghana bauxite is essentially mined at Awaso

(Sefwi) a town in the Western-North of Ghana )is minehas been in operation for over sixty years and plans are farahead to increase the production of bauxite in the comingyears )is development may result in the plant generatingmore waste expected to be over 100000 tons per annumwith a potential risk of inundating the mine site [17])erefore Etuaful and Buamah developed an improvedprotocol for producing alum from the Awaso bauxite waste)e protocol has been found to be environmentally friendlycheaper and less burdensome and produces a high yield ofalum (Aw) [18] Potassium alum is considered by the UnitedStates Food andDrugs Authority as a generally recognized asa safe (GRAS) substance and has been used in food andcosmetics for human use [19]

)is work sought to evaluate the pharmaceutical ap-plication of this locally produced alum in a suppository forthe treatment of hemorrhoids Since alum has been used inlarge amounts for the purification of water for humanconsumption with no noticeable side effects its use forhaemorrhoid treatment will not cause undesirable side ef-fects associated with corticosteroids and NSAIDs )ey canalso be used for a prolonged period due to the low amountthat will be required for treatment Alum is highly hydro-philic and therefore requires a fatty base for its formulation)e suppositories were formulated using theobroma oilshea butter and beeswax Shea butter is locally abundant andcheap with a low melting point As such beeswax wasemployed as a hardening agent )eobroma oil is known tobe a standard fatty base for suppositories but it is costly)erefore combinations of these three available bases wereevaluated as bases for the formulation of suppositories withlocally produced alum )e suppositories were evaluated forquality according to standard specifications and tested fortheir antihemorrhoidal effect in rat models

2 Materials and Methods

21 Materials )e local alum (Aw) was obtained from theCivil Engineering Department of the College of EngineeringKNUST Kumasi White beeswax was obtained from theDepartment of Pharmaceutics KNUST Kumasi )eo-broma oil (cocoa butter) was purchased from Tree of LifeGhana Limited Accra Diclofenac sodium powder wasobtained as a gift from Danadams Pharmaceutical IndustryGhana Shea butter was purchased from Savelugu in thenorthern part of Ghana All other chemical reagents wereobtained from the Department of Pharmaceutics KNUSTKumasi

22 Methods

221 Identification and Authentication of the Alum Sample)e physical characteristics of the alum were determined bythe appearance colour smell feel pH and solubility )epresence of major elements (Al3+ K+ and SO4

2minus) was in-vestigated by qualitative chemical tests

(1) Identification Test of Aluminium Ion (Al3+) One gramof the powdered alum (Aw) was dissolved in 10ml of dis-tilled water in a test tube 01M of sodium hydroxide

2 )e Scientific World Journal

solution (NaOH) was added dropwise to 1ml of the aqueoussolution containing the alum About 1ml of aqueous am-monia (NH3) solution was added to the aqueous solution)e presence of a white precipitate indicated the presence ofaluminium [20] )e procedure was repeated two moretimes

(2) Identification Test of Potassium Ion (K+) A cottonswab was moistened at one end with distilled water )emoistened end of the cotton swab was then dipped into acontainer containing the powdered alum (Aw) and thenintroduced to a nonluminous flame from a Bunsen burner Aviolet colour change of the flame indicated the presence ofpotassium ions present in the alum [20])e experiment wasdone in triplicate

(3) Identification Test of Sulphate Ion (SO42minus) About 1ml

of dilute hydrochloric acid was added to 2ml of the aqueoussolution of the alum 02M barium chloride (BaCl2) solutionwas then added to the resulting solution dropwise )eformation of a white precipitate indicated the presence ofsulphate ion [20] )e experiment was repeated two moretimes

(4) Determination of pH of Alum Solution One gram of thegrounded powder of alum (Aw) was weighed and dissolvedin 10ml of distilled water It was then filtered and the pH ofthe filtrate was determined using a previously calibrated

Eutechreg pH meter (pH 510 pHmVdegC meter Singapore)under room temperature [20] )is test was done intriplicate

(5) Determination of Solubility of Alum in Water )e sol-ubility of the powdered alum (Aw) in water was determinedby weighing accurately 65 g into 100ml of distilled water at25Cplusmn 2degC It was well shaken at time intervals for the first 30minutes )ey were then kept uninterrupted for 2 hours atroom temperature)emixture was filtered and 73ml of thefiltrate was diluted to 300ml )e diluted solution was thenanalyzed by complexometric back titration with ethyl-enediaminetetraacetic acid (EDTA) In this method 10ml ofthe diluted filtrate was pipetted into a conical flask 50ml of001M EDTAwas added and boiled for about 5 minutes)emixture was left to cool to room temperature 5 drops of solochrome black were added to the mixture and a blue colourchange was observed About 1ml of 10 ammonia solutionwas added to the mixture )e resultant solution was thentitrated with 001M zinc sulphate solution until a pinkcolour was observed as an endpoint and the titre value wasrecorded )e difference between the EDTA volume addedand the titre value was then calculated (EDTA volume(ml) ndash titre value of zinc sulphate (ml)) )e amount of alumwas then calculated using the following formulafd1

mass of alum 2373mg times(EDTAvol(ml) minus titre value of zinc sulphate) times dilution factor(DF) (1)

)is experiment was carried out in triplicate [21])e solubility of the powder of the alum (Aw) in hot

water was also determined by weighing accurately 65 g into100ml of distilled water at 50degCplusmn 2degC )e procedure asstated above was followed

(6) Identification of Alum Shea Butter 5eobroma Oil andBeeswax by Infrared Spectroscopy Attenuated total reflec-tion-Fourier transform infrared (ATR-FTIR) spectroscopy(ATR-FTIR spectrometer 200-X SN 200043 USA) wasused to identify the presence of major peaks in the alumshea butter theobroma oil and beeswax in the wavenumberrange of 400 cmminus1 to 4000 cmminus1 and compared with stan-dards )e diamond crystal sensor of the ATR-FTIR wascleaned with isopropanol to get rid of every impurity presenton the sensor that will affect the result With the help of aspatula a little amount of alum powder was placed on thediamond crystal and the spectrum was generated in thestated wavenumber range )e same was done for sheabutter theobroma oil and beeswax

222 Drug-Base Interactions Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopymethod was used to investigate any drug-base interactionsA physical mixture of alum (Aw) and shea butter wasprepared in a 1 1 ratio and placed on the diamond crystaland scanned for the spectrum in the wavenumber range of

400 cmminus1 to 4000 cmminus1 )is was repeated for theobroma oilmixed with alum and beeswax was mixed with alum Againshea butter was mixed with theobroma oil and subsequentlymixed with alum in a ratio of 1 1 1 and the spectrum wasobtained)is was repeated for shea butter with beeswax andalum )e ATR-FTIR spectra were analyzed for possibledrug-base interactions by observing missing peaks elon-gation and shortening of peaks

223 Determination of the Displacement Value of the AlumSix suppositories of each base (shea butter with beeswaxtheobroma oil with beeswax or shea butter with theobromaoil) were prepared and weighed (amg) using a 2 g mold(method explained in detail under Section 224) )ese arereferred to as blank suppositories Six medicated supposi-tories containing 40 of the alum were also prepared for theabove-stated bases and weighed (bmg) )e amount of thebases (cmg) and alum (dmg) in the medicated suppositorywas determined [22] )e displacement value of the alum ina particular base was calculated using the following formula

displacement value d(mg)

a minus c(mg) (2)

224 Preparation of Suppositories Forty suppositories ofeach of the bases and modifications (Table 1) were prepared

)e Scientific World Journal 3

using the hot melt and trituration methods Ten formula-tions were investigated by (1) modifying shea butter withdifferent amounts of beeswax (2) modifying shea butterwith different amounts of theobroma oil and (3) modifyingtheobroma oil with varying amounts of beeswax

Blank suppository using for example shea butter andbeeswax was prepared using the 2 g mold and weighed )edisplacement value stated in Table 2 for shea butter andbeeswax was used to calculate the total amount of baserequired for the formulation of the forty suppositories byusing the following equation [23]

amount of total base(B) (N times y) minus N timesD

DV1113874 1113875 (3)

whereN is the number of suppositories to be formulated y isthe weight of blank suppository (20317 g) D is the amountof drug in one suppository (05 g) and DV is the dis-placement value of base (173) Of the total base 5 con-stituted the beeswax )e constituents of the formulationsare as shown in Table 1

A 2 g suppositorymold (D-7166 Erwema PharmatechnikGermany) was disassembled and washed clean and dried)emold was lubricated with the help of cotton wool and soapspirit)e alum (Aw) was weighed using an analytical balance(SN AE 436647 Adam Equipment UK) )e beeswax plusshea butter base formulations were prepared by first heatingthe beeswax at about 64degC on a water bath (Sanyo OMTOven Gallenkamp UK) until it liquefied completely )eshea butter was shredded weighed and added to the liquefiedbeeswax and stirred steadily Care was taken to preventoverheating the shea butter )e procedure was repeated forthe beeswax plus theobroma oil base formulations but withthe formulations of the theobroma oil and the theobroma oilplus shea butter they were shredded weighed and heatedtogether in a stainless steel container on a water bath at atemperature of 37degC until a uniform mixture was obtained)e alum was incorporated into a little of the base on a warm

tile and then stirred with the rest of the base until a ho-mogeneous mixture was obtained )e molten mass was leftto set and poured into the mold until overfill )e mold wasthen refrigerated for about 30 minutes for solidification )eexcess base was scraped from the top of the mold with a warmspatula )e mold was disassembled and the suppositorieswere removed packed and stored until further use

23 Quality Evaluation of Formulated Suppositories )esuppositories were evaluated in accordance with the re-quirements of the British Pharmacopoeia [24]

231 Physical Characteristics of Suppositories

(1) Sensory Evaluation )e formulated suppositories wereassessed for colour and surface parameters such as textureappearance feel and shape to ensure product-to-productconsistency )e odour of the prepared suppositories wasverified by smelling each of the various formulations andrecorded

(2) Surface Condition )e surfaces of the suppositories wereexamined for brilliance dullness mottling cracks darkregions axial cavities bursts air bubbles and holes andobservations were noted

232 Uniformity of Weight Test on Suppositories Twentysuppositories from each formulation were randomly selectedand collectively weighed )ey were also weighed individ-ually )e mean and individual weight of the suppositorieswere determined as A and B respectively )e individualsuppository weight was deducted from the mean weight ofthe suppositories (A-B) )e percentage deviation of eachsuppository from the mean was also calculated using thefollowing formula

|A minus B|

Atimes 100 (4)

where A is the mean weight of the suppositories and B is theindividual weight

For all weights of suppositories not more than twosuppositories must deviate from the mean weight by more

Table 1 Quantities of alum shea butter theobroma oil andbeeswax used for the formulation of suppositories

FormulationsQuantities (g)

Alum(Aw)

Sheabutter

)eobromaoil Beeswax

BS1 20 6622 349 (5)BS2 20 6272 697 (10)BS3 20 5891 1040 (15)BS4 20 5528 1382 (20)BS5 20 5183 1783 (25)BT 20 6605 348 (5)TH 20 6811

ST1 20 3375(1 part) 3375 (1 part)

ST2 20 4603(2 parts) 2301 (1 part)

ST3 20 5170(3 parts) 1724 (1 part)

BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Stated numbers are basedon the preparation of 40 suppositories (n 40)

Table 2 Physical characteristics of the alum

Characteristics Results alum (Aw)Taste StypticColour WhiteOdour OdourlessSurface appearance Smooth and glassypH 329plusmn 001

Solubility 1367plusmn 001 g100ml (25degC)3080plusmn 001 g100ml (50degC)

Aluminium (Al3+) PresentPotassium (K+) PresentSulphate ions (SO4

2minus) Present)e pH and solubility values are presented by meanplusmn standard deviation(n 3)

4 )e Scientific World Journal

than 5 and none of the suppositories must deviate by morethan 10 [25]

233 Disintegration Tests of Suppositories )e USP tabletdisintegration apparatus (Erweka Type ZT 31 GmbHHeusenstamm Nr 68318 Germany) was used for the testSix suppositories from each batch were placed in the basketrack of the disintegration apparatus and a plastic disk wasplaced on each )e time it took for all six suppositories tomelt or soften at 37degCplusmn 2degC in 1000ml of distilled water wasrecorded )e mean of six determinations and the standarddeviation were calculated

234 Content Uniformity of Suppositories )e drug contentwas determined according to the method used by Baria et al[26] with few modifications Ten individual suppositorieswere randomly selected from the formulations (Table 1) andassayed individually for their drug contents For the assaythe suppositories were weighed individually and theirweights were recorded Each suppository was put in a 100mlbeaker and was dispersed in deionized water (50ml) on awater bath )e resultant mixture was made up to 100mlmark with more deionized water and kept at 50degC )esolution was filtered with a Whatman filter paper with theaid of a funnel into a 200ml conical flask )e filtrate wasanalyzed using the complexometric back titration method asdescribed under the solubility test )is was repeated for theten randomly selected suppositories )e average contentand standard deviation were determined

235 Dissolution Test on Suppositories )e dissolution testwas carried out using the USP apparatus II (Erweka TypeDT6 GmbH Heusenstamm Nr 68045 Germany) )eexperiment was performed using 900ml deionized water ofpH 68 a paddle speed of 50 revolutions per minute and atemperature of 37degCplusmn 05degC At a specified time interval10ml of the dissolution medium was pipetted from thevessel and filtered immediately into a test tube 10ml of freshdissolution medium was withdrawn from the reservoir toreplace the 10ml withdrawn from the dissolution vessel )efiltrate was then diluted with distilled water to the 100mlmark of the volumetric flask and analyzed by com-plexometric titration as described above under the solu-bilitycontent test )e concentration of the alum releasedwas calculated )e percentage release and cumulativepercentage release were then determined)e procedure wasrepeated at specific time intervals of 15 30 45 60 90 120150 and 180 minutes A plot of cumulative percentage drugrelease against time was established

24 Experimental Animals Twenty-five (25) male SpragueDawley rats (5 to 6 months old) were purchased from theAnimal Unit of Noguchi Memorial Institute for MedicalResearch Accra and kept in stainless steel cages of di-mensions 34 cmtimes 57 cmtimes 40 cm at a population of 5 animalsper cage in the animal house of the Department of Phar-macology Faculty of Pharmacy and Pharmaceutical

Sciences KNUST Kumasi to acclimatize for 7 daysCommercial feed (Agricare Kumasi) and water were pro-vided ad libitum throughout the experiment Room tem-perature of 29degC was maintained within the cages and a 12-hour light-dark cycle was maintained using overhead in-candescent illumination [27] All experiments were con-ducted in accordance with protocols from the NationalResearch Council (US) Committee for the Update of theldquoGuide for the Care and Use of Laboratory Animalsrdquo-8thedition (2011) All protocols used were approved by theEthics Committee of the Department of PharmacologyKwame Nkrumah University of Science amp TechnologyKumasi Ghana

25 Evaluation of the Antihemorrhoid Property of the AlumSuppository Evaluation of antihemorrhoidal properties wascarried out as described by Azeemuddin et al [28] with somemodifications To do this Sprague Dawley rats (220ndash240 g)were randomly selected and put into five groups of five (G1to G5 n 5) Group G1 was the naıve (untreated) groupGroups G2 G3 G4 and G5 were pretreated with sterilecotton swabs (4mm diameter) soaked in 100 μL of croton oilinserted into the anus (rectoanal portion 20mm from analopening) and kept for 10 seconds )e cotton swabs wereremoved and thereafter groups G3 G4 and G5 receiveddaily for 5 days bland (05 g vehicle control) diclofenac(15mg positive control) and alum (100mg ST3) sup-positories respectively )e rats were weighed and sacrificedon the fifth day

Rectoanal tissue (20mm in length from the analopening) of each rat was taken off and weighed )e severityof the hemorrhoids was determined using the rectoanalcoefficient (RAC) calculated using the following formula

rectoanal coefficient(RAC) weight of rectoanal tissue(mg)

body weight(g)

(5)

Rectoanal coefficient (RAC) can be defined as the ratio ofthe rectoanal part of the test animal inmilligrams (mg) to thebody weight of the same animal in grams (g))e smaller theRAC value the more efficacious the remedy

Histopathological analysis was carried out on the excisedtissues to study the disease state at themicroscopic level)etissues were fixed in 10 neutral buffered formalin solutionfor examination using a light microscope (Olympus BX51TF Olympus Corporation Tokyo Japan)

26 Statistical Analysis Results on the effect of alum (Aw)suppositories on croton oil-induced hemorrhoids wereexpressed as the meansplusmn standard error of mean (SEM)Statistical significance of the differences between the meanswas determined by one-way analysis of variance (ANOVA)using KruskalndashWallis test followed by Dunnrsquos multiplecomparison test using GraphPad Prism (GraphPad Prismversion 8 forWindows San Diego CA USA) A Plt 005 wasconsidered statistically significant

)e Scientific World Journal 5

3 Results and Discussion

Suppositories consist of a base or a combination of bases(vehicle) and the active pharmaceutical ingredient (drug))e choice of a base depends on the partition coefficient ofthe drug in the base and the biological fluidWhen a drug hasa high vehicle-to-water partition coefficient the tendency toleave the vehicle is minimal and thus the release rate intothe rectal fluid is low )is is not favourable for rapid ab-sorption On the other hand certain lipid solubility is re-quired for penetration through the rectal membrane )eoptimal balance between these two requirements shouldalways be established)us as a general rule a drug with lowfat solubility and high water solubility requires a fatty base asa vehicle for its formulation into a suppository [9 10] Alumis highly water-soluble hence a fatty base was needed for itsformulation Cocoa butter (theobroma oil) and shea butterare fatty bases Cocoa butter is costly while shea butter ischeap and readily available locally but has a low meltingpoint)us to improve upon its melting properties beeswaxwas added as a hardening agent

31 Identification and Authentication of the Alum Sample)e physical test results revealed that the alum was white incolour and odourless with a smooth and glassy surfacetexture It was very hard to be fractured (Figure 1 andTable 2)

)e pH evaluation revealed the alumwas acidic All thesephysical properties complied with the identity of alum by theBritish Pharmacopoeia [20] Identification test is vital indetermining the authenticity of any substance )us inorder to determine how authentic the alum was variousidentification tests as stated in the British Pharmacopoeiawere carried out )e alum reacted with sodium hydroxideto produce a white precipitate [20] )is indicated thepresence of aluminium ions )e resultant solution reactedwith ammonia solution to produce a gelatinous precipitateconfirming the presence of aluminium in alum)e additionof dilute hydrochloric acid to alum produces white pre-cipitates to indicate the presence of sulphate ion Uponaddition of 2M barium chloride to the resulting solution thewhite precipitate was maintained confirming the presence ofthe sulphate ions Introducing alum to a nonluminous flameto produce a pale violet flame indicates the presence ofpotassium

In the current research the alum sample produced asimilar outcome as stated in the British Pharmacopoeia [20]for the identification of alum as well as that observed byBirnin-Yauri and Musa [29]

Solubility is a preformulation parameter that has to beassessed for all drugs It influences the dissolution character-istics of the drug in a dosage form and hence its bioavailabilitySolubility has also been used as one of the criteria for theclassification of drugs according to the BiopharmaceuticsClassification System (BCS) [30] )e solubility test resultsshowed that 1367plusmn001 g and 3080plusmn 001 g of alum com-pletely dissolved in 100ml of distilled water at 25degC and 50degCrespectively )ese values suggest that the sample is freely

soluble in water and its solubility increases with increasingtemperature )e values were however slightly lower thanthose stated in the literature of 14 g100ml (20degC) and 3680 g100ml (50degC) [31] )is difference in solubility may be due tothe source of the alum produced

32 Displacement Value of the Alum Traditionally sup-positories are prepared using suppository molds which cangenerally hold 1 gram or 2 grams of base )at is the volumeof the mold generally remains constant and cannot changeWhenever we add drug or other excipients to the base thedrug occupies some of the space and displaces a certainquantity of base )e displacement value is therefore anindicator of the amount of the base that is displaced toaccommodate the medicament to be incorporated )edisplacement value of a drug must be determined in aparticular base in which it is incorporated It is essential inensuring that the correct amount of drug is contained withina defined quantity of a dosage form )e displacement valueand the amount of drug to be incorporated enable one todetermine the amount of base required for the formulation)e displacement values of alum (Aw) in all suppositoryformulations were evaluated and the results are given inTable 3 )e displacement values were not significantlydifferent for the different bases (Pgt 005)

33 Investigation of PossibleDrug-Base InteractionsUsing FT-IRSpectroscopy Fourier transform infrared (FT-IR) spectros-copy was carried out on the alum powder the theobroma oilbeeswax shea butter andmixtures of these bases to ascertainthe compatibility of the drug substance with the differentbases Figures 2ndash6 show the FT-IR spectra of the alumtheobroma oil beeswax shea butter and different combi-nations respectively In developing a rectal suppositorydosage form it is very essential to carry out drug-base in-teraction studies to help eliminate the issues of incompat-ibility and stability and ensure the release of the drug fromthe base used in the formulations

Figure 1 Powdered alum sample produced from bauxite waste inGhana

6 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

solution (NaOH) was added dropwise to 1ml of the aqueoussolution containing the alum About 1ml of aqueous am-monia (NH3) solution was added to the aqueous solution)e presence of a white precipitate indicated the presence ofaluminium [20] )e procedure was repeated two moretimes

(2) Identification Test of Potassium Ion (K+) A cottonswab was moistened at one end with distilled water )emoistened end of the cotton swab was then dipped into acontainer containing the powdered alum (Aw) and thenintroduced to a nonluminous flame from a Bunsen burner Aviolet colour change of the flame indicated the presence ofpotassium ions present in the alum [20])e experiment wasdone in triplicate

(3) Identification Test of Sulphate Ion (SO42minus) About 1ml

of dilute hydrochloric acid was added to 2ml of the aqueoussolution of the alum 02M barium chloride (BaCl2) solutionwas then added to the resulting solution dropwise )eformation of a white precipitate indicated the presence ofsulphate ion [20] )e experiment was repeated two moretimes

(4) Determination of pH of Alum Solution One gram of thegrounded powder of alum (Aw) was weighed and dissolvedin 10ml of distilled water It was then filtered and the pH ofthe filtrate was determined using a previously calibrated

Eutechreg pH meter (pH 510 pHmVdegC meter Singapore)under room temperature [20] )is test was done intriplicate

(5) Determination of Solubility of Alum in Water )e sol-ubility of the powdered alum (Aw) in water was determinedby weighing accurately 65 g into 100ml of distilled water at25Cplusmn 2degC It was well shaken at time intervals for the first 30minutes )ey were then kept uninterrupted for 2 hours atroom temperature)emixture was filtered and 73ml of thefiltrate was diluted to 300ml )e diluted solution was thenanalyzed by complexometric back titration with ethyl-enediaminetetraacetic acid (EDTA) In this method 10ml ofthe diluted filtrate was pipetted into a conical flask 50ml of001M EDTAwas added and boiled for about 5 minutes)emixture was left to cool to room temperature 5 drops of solochrome black were added to the mixture and a blue colourchange was observed About 1ml of 10 ammonia solutionwas added to the mixture )e resultant solution was thentitrated with 001M zinc sulphate solution until a pinkcolour was observed as an endpoint and the titre value wasrecorded )e difference between the EDTA volume addedand the titre value was then calculated (EDTA volume(ml) ndash titre value of zinc sulphate (ml)) )e amount of alumwas then calculated using the following formulafd1

mass of alum 2373mg times(EDTAvol(ml) minus titre value of zinc sulphate) times dilution factor(DF) (1)

)is experiment was carried out in triplicate [21])e solubility of the powder of the alum (Aw) in hot

water was also determined by weighing accurately 65 g into100ml of distilled water at 50degCplusmn 2degC )e procedure asstated above was followed

(6) Identification of Alum Shea Butter 5eobroma Oil andBeeswax by Infrared Spectroscopy Attenuated total reflec-tion-Fourier transform infrared (ATR-FTIR) spectroscopy(ATR-FTIR spectrometer 200-X SN 200043 USA) wasused to identify the presence of major peaks in the alumshea butter theobroma oil and beeswax in the wavenumberrange of 400 cmminus1 to 4000 cmminus1 and compared with stan-dards )e diamond crystal sensor of the ATR-FTIR wascleaned with isopropanol to get rid of every impurity presenton the sensor that will affect the result With the help of aspatula a little amount of alum powder was placed on thediamond crystal and the spectrum was generated in thestated wavenumber range )e same was done for sheabutter theobroma oil and beeswax

222 Drug-Base Interactions Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopymethod was used to investigate any drug-base interactionsA physical mixture of alum (Aw) and shea butter wasprepared in a 1 1 ratio and placed on the diamond crystaland scanned for the spectrum in the wavenumber range of

400 cmminus1 to 4000 cmminus1 )is was repeated for theobroma oilmixed with alum and beeswax was mixed with alum Againshea butter was mixed with theobroma oil and subsequentlymixed with alum in a ratio of 1 1 1 and the spectrum wasobtained)is was repeated for shea butter with beeswax andalum )e ATR-FTIR spectra were analyzed for possibledrug-base interactions by observing missing peaks elon-gation and shortening of peaks

223 Determination of the Displacement Value of the AlumSix suppositories of each base (shea butter with beeswaxtheobroma oil with beeswax or shea butter with theobromaoil) were prepared and weighed (amg) using a 2 g mold(method explained in detail under Section 224) )ese arereferred to as blank suppositories Six medicated supposi-tories containing 40 of the alum were also prepared for theabove-stated bases and weighed (bmg) )e amount of thebases (cmg) and alum (dmg) in the medicated suppositorywas determined [22] )e displacement value of the alum ina particular base was calculated using the following formula

displacement value d(mg)

a minus c(mg) (2)

224 Preparation of Suppositories Forty suppositories ofeach of the bases and modifications (Table 1) were prepared

)e Scientific World Journal 3

using the hot melt and trituration methods Ten formula-tions were investigated by (1) modifying shea butter withdifferent amounts of beeswax (2) modifying shea butterwith different amounts of theobroma oil and (3) modifyingtheobroma oil with varying amounts of beeswax

Blank suppository using for example shea butter andbeeswax was prepared using the 2 g mold and weighed )edisplacement value stated in Table 2 for shea butter andbeeswax was used to calculate the total amount of baserequired for the formulation of the forty suppositories byusing the following equation [23]

amount of total base(B) (N times y) minus N timesD

DV1113874 1113875 (3)

whereN is the number of suppositories to be formulated y isthe weight of blank suppository (20317 g) D is the amountof drug in one suppository (05 g) and DV is the dis-placement value of base (173) Of the total base 5 con-stituted the beeswax )e constituents of the formulationsare as shown in Table 1

A 2 g suppositorymold (D-7166 Erwema PharmatechnikGermany) was disassembled and washed clean and dried)emold was lubricated with the help of cotton wool and soapspirit)e alum (Aw) was weighed using an analytical balance(SN AE 436647 Adam Equipment UK) )e beeswax plusshea butter base formulations were prepared by first heatingthe beeswax at about 64degC on a water bath (Sanyo OMTOven Gallenkamp UK) until it liquefied completely )eshea butter was shredded weighed and added to the liquefiedbeeswax and stirred steadily Care was taken to preventoverheating the shea butter )e procedure was repeated forthe beeswax plus theobroma oil base formulations but withthe formulations of the theobroma oil and the theobroma oilplus shea butter they were shredded weighed and heatedtogether in a stainless steel container on a water bath at atemperature of 37degC until a uniform mixture was obtained)e alum was incorporated into a little of the base on a warm

tile and then stirred with the rest of the base until a ho-mogeneous mixture was obtained )e molten mass was leftto set and poured into the mold until overfill )e mold wasthen refrigerated for about 30 minutes for solidification )eexcess base was scraped from the top of the mold with a warmspatula )e mold was disassembled and the suppositorieswere removed packed and stored until further use

23 Quality Evaluation of Formulated Suppositories )esuppositories were evaluated in accordance with the re-quirements of the British Pharmacopoeia [24]

231 Physical Characteristics of Suppositories

(1) Sensory Evaluation )e formulated suppositories wereassessed for colour and surface parameters such as textureappearance feel and shape to ensure product-to-productconsistency )e odour of the prepared suppositories wasverified by smelling each of the various formulations andrecorded

(2) Surface Condition )e surfaces of the suppositories wereexamined for brilliance dullness mottling cracks darkregions axial cavities bursts air bubbles and holes andobservations were noted

232 Uniformity of Weight Test on Suppositories Twentysuppositories from each formulation were randomly selectedand collectively weighed )ey were also weighed individ-ually )e mean and individual weight of the suppositorieswere determined as A and B respectively )e individualsuppository weight was deducted from the mean weight ofthe suppositories (A-B) )e percentage deviation of eachsuppository from the mean was also calculated using thefollowing formula

|A minus B|

Atimes 100 (4)

where A is the mean weight of the suppositories and B is theindividual weight

For all weights of suppositories not more than twosuppositories must deviate from the mean weight by more

Table 1 Quantities of alum shea butter theobroma oil andbeeswax used for the formulation of suppositories

FormulationsQuantities (g)

Alum(Aw)

Sheabutter

)eobromaoil Beeswax

BS1 20 6622 349 (5)BS2 20 6272 697 (10)BS3 20 5891 1040 (15)BS4 20 5528 1382 (20)BS5 20 5183 1783 (25)BT 20 6605 348 (5)TH 20 6811

ST1 20 3375(1 part) 3375 (1 part)

ST2 20 4603(2 parts) 2301 (1 part)

ST3 20 5170(3 parts) 1724 (1 part)

BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Stated numbers are basedon the preparation of 40 suppositories (n 40)

Table 2 Physical characteristics of the alum

Characteristics Results alum (Aw)Taste StypticColour WhiteOdour OdourlessSurface appearance Smooth and glassypH 329plusmn 001

Solubility 1367plusmn 001 g100ml (25degC)3080plusmn 001 g100ml (50degC)

Aluminium (Al3+) PresentPotassium (K+) PresentSulphate ions (SO4

2minus) Present)e pH and solubility values are presented by meanplusmn standard deviation(n 3)

4 )e Scientific World Journal

than 5 and none of the suppositories must deviate by morethan 10 [25]

233 Disintegration Tests of Suppositories )e USP tabletdisintegration apparatus (Erweka Type ZT 31 GmbHHeusenstamm Nr 68318 Germany) was used for the testSix suppositories from each batch were placed in the basketrack of the disintegration apparatus and a plastic disk wasplaced on each )e time it took for all six suppositories tomelt or soften at 37degCplusmn 2degC in 1000ml of distilled water wasrecorded )e mean of six determinations and the standarddeviation were calculated

234 Content Uniformity of Suppositories )e drug contentwas determined according to the method used by Baria et al[26] with few modifications Ten individual suppositorieswere randomly selected from the formulations (Table 1) andassayed individually for their drug contents For the assaythe suppositories were weighed individually and theirweights were recorded Each suppository was put in a 100mlbeaker and was dispersed in deionized water (50ml) on awater bath )e resultant mixture was made up to 100mlmark with more deionized water and kept at 50degC )esolution was filtered with a Whatman filter paper with theaid of a funnel into a 200ml conical flask )e filtrate wasanalyzed using the complexometric back titration method asdescribed under the solubility test )is was repeated for theten randomly selected suppositories )e average contentand standard deviation were determined

235 Dissolution Test on Suppositories )e dissolution testwas carried out using the USP apparatus II (Erweka TypeDT6 GmbH Heusenstamm Nr 68045 Germany) )eexperiment was performed using 900ml deionized water ofpH 68 a paddle speed of 50 revolutions per minute and atemperature of 37degCplusmn 05degC At a specified time interval10ml of the dissolution medium was pipetted from thevessel and filtered immediately into a test tube 10ml of freshdissolution medium was withdrawn from the reservoir toreplace the 10ml withdrawn from the dissolution vessel )efiltrate was then diluted with distilled water to the 100mlmark of the volumetric flask and analyzed by com-plexometric titration as described above under the solu-bilitycontent test )e concentration of the alum releasedwas calculated )e percentage release and cumulativepercentage release were then determined)e procedure wasrepeated at specific time intervals of 15 30 45 60 90 120150 and 180 minutes A plot of cumulative percentage drugrelease against time was established

24 Experimental Animals Twenty-five (25) male SpragueDawley rats (5 to 6 months old) were purchased from theAnimal Unit of Noguchi Memorial Institute for MedicalResearch Accra and kept in stainless steel cages of di-mensions 34 cmtimes 57 cmtimes 40 cm at a population of 5 animalsper cage in the animal house of the Department of Phar-macology Faculty of Pharmacy and Pharmaceutical

Sciences KNUST Kumasi to acclimatize for 7 daysCommercial feed (Agricare Kumasi) and water were pro-vided ad libitum throughout the experiment Room tem-perature of 29degC was maintained within the cages and a 12-hour light-dark cycle was maintained using overhead in-candescent illumination [27] All experiments were con-ducted in accordance with protocols from the NationalResearch Council (US) Committee for the Update of theldquoGuide for the Care and Use of Laboratory Animalsrdquo-8thedition (2011) All protocols used were approved by theEthics Committee of the Department of PharmacologyKwame Nkrumah University of Science amp TechnologyKumasi Ghana

25 Evaluation of the Antihemorrhoid Property of the AlumSuppository Evaluation of antihemorrhoidal properties wascarried out as described by Azeemuddin et al [28] with somemodifications To do this Sprague Dawley rats (220ndash240 g)were randomly selected and put into five groups of five (G1to G5 n 5) Group G1 was the naıve (untreated) groupGroups G2 G3 G4 and G5 were pretreated with sterilecotton swabs (4mm diameter) soaked in 100 μL of croton oilinserted into the anus (rectoanal portion 20mm from analopening) and kept for 10 seconds )e cotton swabs wereremoved and thereafter groups G3 G4 and G5 receiveddaily for 5 days bland (05 g vehicle control) diclofenac(15mg positive control) and alum (100mg ST3) sup-positories respectively )e rats were weighed and sacrificedon the fifth day

Rectoanal tissue (20mm in length from the analopening) of each rat was taken off and weighed )e severityof the hemorrhoids was determined using the rectoanalcoefficient (RAC) calculated using the following formula

rectoanal coefficient(RAC) weight of rectoanal tissue(mg)

body weight(g)

(5)

Rectoanal coefficient (RAC) can be defined as the ratio ofthe rectoanal part of the test animal inmilligrams (mg) to thebody weight of the same animal in grams (g))e smaller theRAC value the more efficacious the remedy

Histopathological analysis was carried out on the excisedtissues to study the disease state at themicroscopic level)etissues were fixed in 10 neutral buffered formalin solutionfor examination using a light microscope (Olympus BX51TF Olympus Corporation Tokyo Japan)

26 Statistical Analysis Results on the effect of alum (Aw)suppositories on croton oil-induced hemorrhoids wereexpressed as the meansplusmn standard error of mean (SEM)Statistical significance of the differences between the meanswas determined by one-way analysis of variance (ANOVA)using KruskalndashWallis test followed by Dunnrsquos multiplecomparison test using GraphPad Prism (GraphPad Prismversion 8 forWindows San Diego CA USA) A Plt 005 wasconsidered statistically significant

)e Scientific World Journal 5

3 Results and Discussion

Suppositories consist of a base or a combination of bases(vehicle) and the active pharmaceutical ingredient (drug))e choice of a base depends on the partition coefficient ofthe drug in the base and the biological fluidWhen a drug hasa high vehicle-to-water partition coefficient the tendency toleave the vehicle is minimal and thus the release rate intothe rectal fluid is low )is is not favourable for rapid ab-sorption On the other hand certain lipid solubility is re-quired for penetration through the rectal membrane )eoptimal balance between these two requirements shouldalways be established)us as a general rule a drug with lowfat solubility and high water solubility requires a fatty base asa vehicle for its formulation into a suppository [9 10] Alumis highly water-soluble hence a fatty base was needed for itsformulation Cocoa butter (theobroma oil) and shea butterare fatty bases Cocoa butter is costly while shea butter ischeap and readily available locally but has a low meltingpoint)us to improve upon its melting properties beeswaxwas added as a hardening agent

31 Identification and Authentication of the Alum Sample)e physical test results revealed that the alum was white incolour and odourless with a smooth and glassy surfacetexture It was very hard to be fractured (Figure 1 andTable 2)

)e pH evaluation revealed the alumwas acidic All thesephysical properties complied with the identity of alum by theBritish Pharmacopoeia [20] Identification test is vital indetermining the authenticity of any substance )us inorder to determine how authentic the alum was variousidentification tests as stated in the British Pharmacopoeiawere carried out )e alum reacted with sodium hydroxideto produce a white precipitate [20] )is indicated thepresence of aluminium ions )e resultant solution reactedwith ammonia solution to produce a gelatinous precipitateconfirming the presence of aluminium in alum)e additionof dilute hydrochloric acid to alum produces white pre-cipitates to indicate the presence of sulphate ion Uponaddition of 2M barium chloride to the resulting solution thewhite precipitate was maintained confirming the presence ofthe sulphate ions Introducing alum to a nonluminous flameto produce a pale violet flame indicates the presence ofpotassium

In the current research the alum sample produced asimilar outcome as stated in the British Pharmacopoeia [20]for the identification of alum as well as that observed byBirnin-Yauri and Musa [29]

Solubility is a preformulation parameter that has to beassessed for all drugs It influences the dissolution character-istics of the drug in a dosage form and hence its bioavailabilitySolubility has also been used as one of the criteria for theclassification of drugs according to the BiopharmaceuticsClassification System (BCS) [30] )e solubility test resultsshowed that 1367plusmn001 g and 3080plusmn 001 g of alum com-pletely dissolved in 100ml of distilled water at 25degC and 50degCrespectively )ese values suggest that the sample is freely

soluble in water and its solubility increases with increasingtemperature )e values were however slightly lower thanthose stated in the literature of 14 g100ml (20degC) and 3680 g100ml (50degC) [31] )is difference in solubility may be due tothe source of the alum produced

32 Displacement Value of the Alum Traditionally sup-positories are prepared using suppository molds which cangenerally hold 1 gram or 2 grams of base )at is the volumeof the mold generally remains constant and cannot changeWhenever we add drug or other excipients to the base thedrug occupies some of the space and displaces a certainquantity of base )e displacement value is therefore anindicator of the amount of the base that is displaced toaccommodate the medicament to be incorporated )edisplacement value of a drug must be determined in aparticular base in which it is incorporated It is essential inensuring that the correct amount of drug is contained withina defined quantity of a dosage form )e displacement valueand the amount of drug to be incorporated enable one todetermine the amount of base required for the formulation)e displacement values of alum (Aw) in all suppositoryformulations were evaluated and the results are given inTable 3 )e displacement values were not significantlydifferent for the different bases (Pgt 005)

33 Investigation of PossibleDrug-Base InteractionsUsing FT-IRSpectroscopy Fourier transform infrared (FT-IR) spectros-copy was carried out on the alum powder the theobroma oilbeeswax shea butter andmixtures of these bases to ascertainthe compatibility of the drug substance with the differentbases Figures 2ndash6 show the FT-IR spectra of the alumtheobroma oil beeswax shea butter and different combi-nations respectively In developing a rectal suppositorydosage form it is very essential to carry out drug-base in-teraction studies to help eliminate the issues of incompat-ibility and stability and ensure the release of the drug fromthe base used in the formulations

Figure 1 Powdered alum sample produced from bauxite waste inGhana

6 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

using the hot melt and trituration methods Ten formula-tions were investigated by (1) modifying shea butter withdifferent amounts of beeswax (2) modifying shea butterwith different amounts of theobroma oil and (3) modifyingtheobroma oil with varying amounts of beeswax

Blank suppository using for example shea butter andbeeswax was prepared using the 2 g mold and weighed )edisplacement value stated in Table 2 for shea butter andbeeswax was used to calculate the total amount of baserequired for the formulation of the forty suppositories byusing the following equation [23]

amount of total base(B) (N times y) minus N timesD

DV1113874 1113875 (3)

whereN is the number of suppositories to be formulated y isthe weight of blank suppository (20317 g) D is the amountof drug in one suppository (05 g) and DV is the dis-placement value of base (173) Of the total base 5 con-stituted the beeswax )e constituents of the formulationsare as shown in Table 1

A 2 g suppositorymold (D-7166 Erwema PharmatechnikGermany) was disassembled and washed clean and dried)emold was lubricated with the help of cotton wool and soapspirit)e alum (Aw) was weighed using an analytical balance(SN AE 436647 Adam Equipment UK) )e beeswax plusshea butter base formulations were prepared by first heatingthe beeswax at about 64degC on a water bath (Sanyo OMTOven Gallenkamp UK) until it liquefied completely )eshea butter was shredded weighed and added to the liquefiedbeeswax and stirred steadily Care was taken to preventoverheating the shea butter )e procedure was repeated forthe beeswax plus theobroma oil base formulations but withthe formulations of the theobroma oil and the theobroma oilplus shea butter they were shredded weighed and heatedtogether in a stainless steel container on a water bath at atemperature of 37degC until a uniform mixture was obtained)e alum was incorporated into a little of the base on a warm

tile and then stirred with the rest of the base until a ho-mogeneous mixture was obtained )e molten mass was leftto set and poured into the mold until overfill )e mold wasthen refrigerated for about 30 minutes for solidification )eexcess base was scraped from the top of the mold with a warmspatula )e mold was disassembled and the suppositorieswere removed packed and stored until further use

23 Quality Evaluation of Formulated Suppositories )esuppositories were evaluated in accordance with the re-quirements of the British Pharmacopoeia [24]

231 Physical Characteristics of Suppositories

(1) Sensory Evaluation )e formulated suppositories wereassessed for colour and surface parameters such as textureappearance feel and shape to ensure product-to-productconsistency )e odour of the prepared suppositories wasverified by smelling each of the various formulations andrecorded

(2) Surface Condition )e surfaces of the suppositories wereexamined for brilliance dullness mottling cracks darkregions axial cavities bursts air bubbles and holes andobservations were noted

232 Uniformity of Weight Test on Suppositories Twentysuppositories from each formulation were randomly selectedand collectively weighed )ey were also weighed individ-ually )e mean and individual weight of the suppositorieswere determined as A and B respectively )e individualsuppository weight was deducted from the mean weight ofthe suppositories (A-B) )e percentage deviation of eachsuppository from the mean was also calculated using thefollowing formula

|A minus B|

Atimes 100 (4)

where A is the mean weight of the suppositories and B is theindividual weight

For all weights of suppositories not more than twosuppositories must deviate from the mean weight by more

Table 1 Quantities of alum shea butter theobroma oil andbeeswax used for the formulation of suppositories

FormulationsQuantities (g)

Alum(Aw)

Sheabutter

)eobromaoil Beeswax

BS1 20 6622 349 (5)BS2 20 6272 697 (10)BS3 20 5891 1040 (15)BS4 20 5528 1382 (20)BS5 20 5183 1783 (25)BT 20 6605 348 (5)TH 20 6811

ST1 20 3375(1 part) 3375 (1 part)

ST2 20 4603(2 parts) 2301 (1 part)

ST3 20 5170(3 parts) 1724 (1 part)

BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Stated numbers are basedon the preparation of 40 suppositories (n 40)

Table 2 Physical characteristics of the alum

Characteristics Results alum (Aw)Taste StypticColour WhiteOdour OdourlessSurface appearance Smooth and glassypH 329plusmn 001

Solubility 1367plusmn 001 g100ml (25degC)3080plusmn 001 g100ml (50degC)

Aluminium (Al3+) PresentPotassium (K+) PresentSulphate ions (SO4

2minus) Present)e pH and solubility values are presented by meanplusmn standard deviation(n 3)

4 )e Scientific World Journal

than 5 and none of the suppositories must deviate by morethan 10 [25]

233 Disintegration Tests of Suppositories )e USP tabletdisintegration apparatus (Erweka Type ZT 31 GmbHHeusenstamm Nr 68318 Germany) was used for the testSix suppositories from each batch were placed in the basketrack of the disintegration apparatus and a plastic disk wasplaced on each )e time it took for all six suppositories tomelt or soften at 37degCplusmn 2degC in 1000ml of distilled water wasrecorded )e mean of six determinations and the standarddeviation were calculated

234 Content Uniformity of Suppositories )e drug contentwas determined according to the method used by Baria et al[26] with few modifications Ten individual suppositorieswere randomly selected from the formulations (Table 1) andassayed individually for their drug contents For the assaythe suppositories were weighed individually and theirweights were recorded Each suppository was put in a 100mlbeaker and was dispersed in deionized water (50ml) on awater bath )e resultant mixture was made up to 100mlmark with more deionized water and kept at 50degC )esolution was filtered with a Whatman filter paper with theaid of a funnel into a 200ml conical flask )e filtrate wasanalyzed using the complexometric back titration method asdescribed under the solubility test )is was repeated for theten randomly selected suppositories )e average contentand standard deviation were determined

235 Dissolution Test on Suppositories )e dissolution testwas carried out using the USP apparatus II (Erweka TypeDT6 GmbH Heusenstamm Nr 68045 Germany) )eexperiment was performed using 900ml deionized water ofpH 68 a paddle speed of 50 revolutions per minute and atemperature of 37degCplusmn 05degC At a specified time interval10ml of the dissolution medium was pipetted from thevessel and filtered immediately into a test tube 10ml of freshdissolution medium was withdrawn from the reservoir toreplace the 10ml withdrawn from the dissolution vessel )efiltrate was then diluted with distilled water to the 100mlmark of the volumetric flask and analyzed by com-plexometric titration as described above under the solu-bilitycontent test )e concentration of the alum releasedwas calculated )e percentage release and cumulativepercentage release were then determined)e procedure wasrepeated at specific time intervals of 15 30 45 60 90 120150 and 180 minutes A plot of cumulative percentage drugrelease against time was established

24 Experimental Animals Twenty-five (25) male SpragueDawley rats (5 to 6 months old) were purchased from theAnimal Unit of Noguchi Memorial Institute for MedicalResearch Accra and kept in stainless steel cages of di-mensions 34 cmtimes 57 cmtimes 40 cm at a population of 5 animalsper cage in the animal house of the Department of Phar-macology Faculty of Pharmacy and Pharmaceutical

Sciences KNUST Kumasi to acclimatize for 7 daysCommercial feed (Agricare Kumasi) and water were pro-vided ad libitum throughout the experiment Room tem-perature of 29degC was maintained within the cages and a 12-hour light-dark cycle was maintained using overhead in-candescent illumination [27] All experiments were con-ducted in accordance with protocols from the NationalResearch Council (US) Committee for the Update of theldquoGuide for the Care and Use of Laboratory Animalsrdquo-8thedition (2011) All protocols used were approved by theEthics Committee of the Department of PharmacologyKwame Nkrumah University of Science amp TechnologyKumasi Ghana

25 Evaluation of the Antihemorrhoid Property of the AlumSuppository Evaluation of antihemorrhoidal properties wascarried out as described by Azeemuddin et al [28] with somemodifications To do this Sprague Dawley rats (220ndash240 g)were randomly selected and put into five groups of five (G1to G5 n 5) Group G1 was the naıve (untreated) groupGroups G2 G3 G4 and G5 were pretreated with sterilecotton swabs (4mm diameter) soaked in 100 μL of croton oilinserted into the anus (rectoanal portion 20mm from analopening) and kept for 10 seconds )e cotton swabs wereremoved and thereafter groups G3 G4 and G5 receiveddaily for 5 days bland (05 g vehicle control) diclofenac(15mg positive control) and alum (100mg ST3) sup-positories respectively )e rats were weighed and sacrificedon the fifth day

Rectoanal tissue (20mm in length from the analopening) of each rat was taken off and weighed )e severityof the hemorrhoids was determined using the rectoanalcoefficient (RAC) calculated using the following formula

rectoanal coefficient(RAC) weight of rectoanal tissue(mg)

body weight(g)

(5)

Rectoanal coefficient (RAC) can be defined as the ratio ofthe rectoanal part of the test animal inmilligrams (mg) to thebody weight of the same animal in grams (g))e smaller theRAC value the more efficacious the remedy

Histopathological analysis was carried out on the excisedtissues to study the disease state at themicroscopic level)etissues were fixed in 10 neutral buffered formalin solutionfor examination using a light microscope (Olympus BX51TF Olympus Corporation Tokyo Japan)

26 Statistical Analysis Results on the effect of alum (Aw)suppositories on croton oil-induced hemorrhoids wereexpressed as the meansplusmn standard error of mean (SEM)Statistical significance of the differences between the meanswas determined by one-way analysis of variance (ANOVA)using KruskalndashWallis test followed by Dunnrsquos multiplecomparison test using GraphPad Prism (GraphPad Prismversion 8 forWindows San Diego CA USA) A Plt 005 wasconsidered statistically significant

)e Scientific World Journal 5

3 Results and Discussion

Suppositories consist of a base or a combination of bases(vehicle) and the active pharmaceutical ingredient (drug))e choice of a base depends on the partition coefficient ofthe drug in the base and the biological fluidWhen a drug hasa high vehicle-to-water partition coefficient the tendency toleave the vehicle is minimal and thus the release rate intothe rectal fluid is low )is is not favourable for rapid ab-sorption On the other hand certain lipid solubility is re-quired for penetration through the rectal membrane )eoptimal balance between these two requirements shouldalways be established)us as a general rule a drug with lowfat solubility and high water solubility requires a fatty base asa vehicle for its formulation into a suppository [9 10] Alumis highly water-soluble hence a fatty base was needed for itsformulation Cocoa butter (theobroma oil) and shea butterare fatty bases Cocoa butter is costly while shea butter ischeap and readily available locally but has a low meltingpoint)us to improve upon its melting properties beeswaxwas added as a hardening agent

31 Identification and Authentication of the Alum Sample)e physical test results revealed that the alum was white incolour and odourless with a smooth and glassy surfacetexture It was very hard to be fractured (Figure 1 andTable 2)

)e pH evaluation revealed the alumwas acidic All thesephysical properties complied with the identity of alum by theBritish Pharmacopoeia [20] Identification test is vital indetermining the authenticity of any substance )us inorder to determine how authentic the alum was variousidentification tests as stated in the British Pharmacopoeiawere carried out )e alum reacted with sodium hydroxideto produce a white precipitate [20] )is indicated thepresence of aluminium ions )e resultant solution reactedwith ammonia solution to produce a gelatinous precipitateconfirming the presence of aluminium in alum)e additionof dilute hydrochloric acid to alum produces white pre-cipitates to indicate the presence of sulphate ion Uponaddition of 2M barium chloride to the resulting solution thewhite precipitate was maintained confirming the presence ofthe sulphate ions Introducing alum to a nonluminous flameto produce a pale violet flame indicates the presence ofpotassium

In the current research the alum sample produced asimilar outcome as stated in the British Pharmacopoeia [20]for the identification of alum as well as that observed byBirnin-Yauri and Musa [29]

Solubility is a preformulation parameter that has to beassessed for all drugs It influences the dissolution character-istics of the drug in a dosage form and hence its bioavailabilitySolubility has also been used as one of the criteria for theclassification of drugs according to the BiopharmaceuticsClassification System (BCS) [30] )e solubility test resultsshowed that 1367plusmn001 g and 3080plusmn 001 g of alum com-pletely dissolved in 100ml of distilled water at 25degC and 50degCrespectively )ese values suggest that the sample is freely

soluble in water and its solubility increases with increasingtemperature )e values were however slightly lower thanthose stated in the literature of 14 g100ml (20degC) and 3680 g100ml (50degC) [31] )is difference in solubility may be due tothe source of the alum produced

32 Displacement Value of the Alum Traditionally sup-positories are prepared using suppository molds which cangenerally hold 1 gram or 2 grams of base )at is the volumeof the mold generally remains constant and cannot changeWhenever we add drug or other excipients to the base thedrug occupies some of the space and displaces a certainquantity of base )e displacement value is therefore anindicator of the amount of the base that is displaced toaccommodate the medicament to be incorporated )edisplacement value of a drug must be determined in aparticular base in which it is incorporated It is essential inensuring that the correct amount of drug is contained withina defined quantity of a dosage form )e displacement valueand the amount of drug to be incorporated enable one todetermine the amount of base required for the formulation)e displacement values of alum (Aw) in all suppositoryformulations were evaluated and the results are given inTable 3 )e displacement values were not significantlydifferent for the different bases (Pgt 005)

33 Investigation of PossibleDrug-Base InteractionsUsing FT-IRSpectroscopy Fourier transform infrared (FT-IR) spectros-copy was carried out on the alum powder the theobroma oilbeeswax shea butter andmixtures of these bases to ascertainthe compatibility of the drug substance with the differentbases Figures 2ndash6 show the FT-IR spectra of the alumtheobroma oil beeswax shea butter and different combi-nations respectively In developing a rectal suppositorydosage form it is very essential to carry out drug-base in-teraction studies to help eliminate the issues of incompat-ibility and stability and ensure the release of the drug fromthe base used in the formulations

Figure 1 Powdered alum sample produced from bauxite waste inGhana

6 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

than 5 and none of the suppositories must deviate by morethan 10 [25]

233 Disintegration Tests of Suppositories )e USP tabletdisintegration apparatus (Erweka Type ZT 31 GmbHHeusenstamm Nr 68318 Germany) was used for the testSix suppositories from each batch were placed in the basketrack of the disintegration apparatus and a plastic disk wasplaced on each )e time it took for all six suppositories tomelt or soften at 37degCplusmn 2degC in 1000ml of distilled water wasrecorded )e mean of six determinations and the standarddeviation were calculated

234 Content Uniformity of Suppositories )e drug contentwas determined according to the method used by Baria et al[26] with few modifications Ten individual suppositorieswere randomly selected from the formulations (Table 1) andassayed individually for their drug contents For the assaythe suppositories were weighed individually and theirweights were recorded Each suppository was put in a 100mlbeaker and was dispersed in deionized water (50ml) on awater bath )e resultant mixture was made up to 100mlmark with more deionized water and kept at 50degC )esolution was filtered with a Whatman filter paper with theaid of a funnel into a 200ml conical flask )e filtrate wasanalyzed using the complexometric back titration method asdescribed under the solubility test )is was repeated for theten randomly selected suppositories )e average contentand standard deviation were determined

235 Dissolution Test on Suppositories )e dissolution testwas carried out using the USP apparatus II (Erweka TypeDT6 GmbH Heusenstamm Nr 68045 Germany) )eexperiment was performed using 900ml deionized water ofpH 68 a paddle speed of 50 revolutions per minute and atemperature of 37degCplusmn 05degC At a specified time interval10ml of the dissolution medium was pipetted from thevessel and filtered immediately into a test tube 10ml of freshdissolution medium was withdrawn from the reservoir toreplace the 10ml withdrawn from the dissolution vessel )efiltrate was then diluted with distilled water to the 100mlmark of the volumetric flask and analyzed by com-plexometric titration as described above under the solu-bilitycontent test )e concentration of the alum releasedwas calculated )e percentage release and cumulativepercentage release were then determined)e procedure wasrepeated at specific time intervals of 15 30 45 60 90 120150 and 180 minutes A plot of cumulative percentage drugrelease against time was established

24 Experimental Animals Twenty-five (25) male SpragueDawley rats (5 to 6 months old) were purchased from theAnimal Unit of Noguchi Memorial Institute for MedicalResearch Accra and kept in stainless steel cages of di-mensions 34 cmtimes 57 cmtimes 40 cm at a population of 5 animalsper cage in the animal house of the Department of Phar-macology Faculty of Pharmacy and Pharmaceutical

Sciences KNUST Kumasi to acclimatize for 7 daysCommercial feed (Agricare Kumasi) and water were pro-vided ad libitum throughout the experiment Room tem-perature of 29degC was maintained within the cages and a 12-hour light-dark cycle was maintained using overhead in-candescent illumination [27] All experiments were con-ducted in accordance with protocols from the NationalResearch Council (US) Committee for the Update of theldquoGuide for the Care and Use of Laboratory Animalsrdquo-8thedition (2011) All protocols used were approved by theEthics Committee of the Department of PharmacologyKwame Nkrumah University of Science amp TechnologyKumasi Ghana

25 Evaluation of the Antihemorrhoid Property of the AlumSuppository Evaluation of antihemorrhoidal properties wascarried out as described by Azeemuddin et al [28] with somemodifications To do this Sprague Dawley rats (220ndash240 g)were randomly selected and put into five groups of five (G1to G5 n 5) Group G1 was the naıve (untreated) groupGroups G2 G3 G4 and G5 were pretreated with sterilecotton swabs (4mm diameter) soaked in 100 μL of croton oilinserted into the anus (rectoanal portion 20mm from analopening) and kept for 10 seconds )e cotton swabs wereremoved and thereafter groups G3 G4 and G5 receiveddaily for 5 days bland (05 g vehicle control) diclofenac(15mg positive control) and alum (100mg ST3) sup-positories respectively )e rats were weighed and sacrificedon the fifth day

Rectoanal tissue (20mm in length from the analopening) of each rat was taken off and weighed )e severityof the hemorrhoids was determined using the rectoanalcoefficient (RAC) calculated using the following formula

rectoanal coefficient(RAC) weight of rectoanal tissue(mg)

body weight(g)

(5)

Rectoanal coefficient (RAC) can be defined as the ratio ofthe rectoanal part of the test animal inmilligrams (mg) to thebody weight of the same animal in grams (g))e smaller theRAC value the more efficacious the remedy

Histopathological analysis was carried out on the excisedtissues to study the disease state at themicroscopic level)etissues were fixed in 10 neutral buffered formalin solutionfor examination using a light microscope (Olympus BX51TF Olympus Corporation Tokyo Japan)

26 Statistical Analysis Results on the effect of alum (Aw)suppositories on croton oil-induced hemorrhoids wereexpressed as the meansplusmn standard error of mean (SEM)Statistical significance of the differences between the meanswas determined by one-way analysis of variance (ANOVA)using KruskalndashWallis test followed by Dunnrsquos multiplecomparison test using GraphPad Prism (GraphPad Prismversion 8 forWindows San Diego CA USA) A Plt 005 wasconsidered statistically significant

)e Scientific World Journal 5

3 Results and Discussion

Suppositories consist of a base or a combination of bases(vehicle) and the active pharmaceutical ingredient (drug))e choice of a base depends on the partition coefficient ofthe drug in the base and the biological fluidWhen a drug hasa high vehicle-to-water partition coefficient the tendency toleave the vehicle is minimal and thus the release rate intothe rectal fluid is low )is is not favourable for rapid ab-sorption On the other hand certain lipid solubility is re-quired for penetration through the rectal membrane )eoptimal balance between these two requirements shouldalways be established)us as a general rule a drug with lowfat solubility and high water solubility requires a fatty base asa vehicle for its formulation into a suppository [9 10] Alumis highly water-soluble hence a fatty base was needed for itsformulation Cocoa butter (theobroma oil) and shea butterare fatty bases Cocoa butter is costly while shea butter ischeap and readily available locally but has a low meltingpoint)us to improve upon its melting properties beeswaxwas added as a hardening agent

31 Identification and Authentication of the Alum Sample)e physical test results revealed that the alum was white incolour and odourless with a smooth and glassy surfacetexture It was very hard to be fractured (Figure 1 andTable 2)

)e pH evaluation revealed the alumwas acidic All thesephysical properties complied with the identity of alum by theBritish Pharmacopoeia [20] Identification test is vital indetermining the authenticity of any substance )us inorder to determine how authentic the alum was variousidentification tests as stated in the British Pharmacopoeiawere carried out )e alum reacted with sodium hydroxideto produce a white precipitate [20] )is indicated thepresence of aluminium ions )e resultant solution reactedwith ammonia solution to produce a gelatinous precipitateconfirming the presence of aluminium in alum)e additionof dilute hydrochloric acid to alum produces white pre-cipitates to indicate the presence of sulphate ion Uponaddition of 2M barium chloride to the resulting solution thewhite precipitate was maintained confirming the presence ofthe sulphate ions Introducing alum to a nonluminous flameto produce a pale violet flame indicates the presence ofpotassium

In the current research the alum sample produced asimilar outcome as stated in the British Pharmacopoeia [20]for the identification of alum as well as that observed byBirnin-Yauri and Musa [29]

Solubility is a preformulation parameter that has to beassessed for all drugs It influences the dissolution character-istics of the drug in a dosage form and hence its bioavailabilitySolubility has also been used as one of the criteria for theclassification of drugs according to the BiopharmaceuticsClassification System (BCS) [30] )e solubility test resultsshowed that 1367plusmn001 g and 3080plusmn 001 g of alum com-pletely dissolved in 100ml of distilled water at 25degC and 50degCrespectively )ese values suggest that the sample is freely

soluble in water and its solubility increases with increasingtemperature )e values were however slightly lower thanthose stated in the literature of 14 g100ml (20degC) and 3680 g100ml (50degC) [31] )is difference in solubility may be due tothe source of the alum produced

32 Displacement Value of the Alum Traditionally sup-positories are prepared using suppository molds which cangenerally hold 1 gram or 2 grams of base )at is the volumeof the mold generally remains constant and cannot changeWhenever we add drug or other excipients to the base thedrug occupies some of the space and displaces a certainquantity of base )e displacement value is therefore anindicator of the amount of the base that is displaced toaccommodate the medicament to be incorporated )edisplacement value of a drug must be determined in aparticular base in which it is incorporated It is essential inensuring that the correct amount of drug is contained withina defined quantity of a dosage form )e displacement valueand the amount of drug to be incorporated enable one todetermine the amount of base required for the formulation)e displacement values of alum (Aw) in all suppositoryformulations were evaluated and the results are given inTable 3 )e displacement values were not significantlydifferent for the different bases (Pgt 005)

33 Investigation of PossibleDrug-Base InteractionsUsing FT-IRSpectroscopy Fourier transform infrared (FT-IR) spectros-copy was carried out on the alum powder the theobroma oilbeeswax shea butter andmixtures of these bases to ascertainthe compatibility of the drug substance with the differentbases Figures 2ndash6 show the FT-IR spectra of the alumtheobroma oil beeswax shea butter and different combi-nations respectively In developing a rectal suppositorydosage form it is very essential to carry out drug-base in-teraction studies to help eliminate the issues of incompat-ibility and stability and ensure the release of the drug fromthe base used in the formulations

Figure 1 Powdered alum sample produced from bauxite waste inGhana

6 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

3 Results and Discussion

Suppositories consist of a base or a combination of bases(vehicle) and the active pharmaceutical ingredient (drug))e choice of a base depends on the partition coefficient ofthe drug in the base and the biological fluidWhen a drug hasa high vehicle-to-water partition coefficient the tendency toleave the vehicle is minimal and thus the release rate intothe rectal fluid is low )is is not favourable for rapid ab-sorption On the other hand certain lipid solubility is re-quired for penetration through the rectal membrane )eoptimal balance between these two requirements shouldalways be established)us as a general rule a drug with lowfat solubility and high water solubility requires a fatty base asa vehicle for its formulation into a suppository [9 10] Alumis highly water-soluble hence a fatty base was needed for itsformulation Cocoa butter (theobroma oil) and shea butterare fatty bases Cocoa butter is costly while shea butter ischeap and readily available locally but has a low meltingpoint)us to improve upon its melting properties beeswaxwas added as a hardening agent

31 Identification and Authentication of the Alum Sample)e physical test results revealed that the alum was white incolour and odourless with a smooth and glassy surfacetexture It was very hard to be fractured (Figure 1 andTable 2)

)e pH evaluation revealed the alumwas acidic All thesephysical properties complied with the identity of alum by theBritish Pharmacopoeia [20] Identification test is vital indetermining the authenticity of any substance )us inorder to determine how authentic the alum was variousidentification tests as stated in the British Pharmacopoeiawere carried out )e alum reacted with sodium hydroxideto produce a white precipitate [20] )is indicated thepresence of aluminium ions )e resultant solution reactedwith ammonia solution to produce a gelatinous precipitateconfirming the presence of aluminium in alum)e additionof dilute hydrochloric acid to alum produces white pre-cipitates to indicate the presence of sulphate ion Uponaddition of 2M barium chloride to the resulting solution thewhite precipitate was maintained confirming the presence ofthe sulphate ions Introducing alum to a nonluminous flameto produce a pale violet flame indicates the presence ofpotassium

In the current research the alum sample produced asimilar outcome as stated in the British Pharmacopoeia [20]for the identification of alum as well as that observed byBirnin-Yauri and Musa [29]

Solubility is a preformulation parameter that has to beassessed for all drugs It influences the dissolution character-istics of the drug in a dosage form and hence its bioavailabilitySolubility has also been used as one of the criteria for theclassification of drugs according to the BiopharmaceuticsClassification System (BCS) [30] )e solubility test resultsshowed that 1367plusmn001 g and 3080plusmn 001 g of alum com-pletely dissolved in 100ml of distilled water at 25degC and 50degCrespectively )ese values suggest that the sample is freely

soluble in water and its solubility increases with increasingtemperature )e values were however slightly lower thanthose stated in the literature of 14 g100ml (20degC) and 3680 g100ml (50degC) [31] )is difference in solubility may be due tothe source of the alum produced

32 Displacement Value of the Alum Traditionally sup-positories are prepared using suppository molds which cangenerally hold 1 gram or 2 grams of base )at is the volumeof the mold generally remains constant and cannot changeWhenever we add drug or other excipients to the base thedrug occupies some of the space and displaces a certainquantity of base )e displacement value is therefore anindicator of the amount of the base that is displaced toaccommodate the medicament to be incorporated )edisplacement value of a drug must be determined in aparticular base in which it is incorporated It is essential inensuring that the correct amount of drug is contained withina defined quantity of a dosage form )e displacement valueand the amount of drug to be incorporated enable one todetermine the amount of base required for the formulation)e displacement values of alum (Aw) in all suppositoryformulations were evaluated and the results are given inTable 3 )e displacement values were not significantlydifferent for the different bases (Pgt 005)

33 Investigation of PossibleDrug-Base InteractionsUsing FT-IRSpectroscopy Fourier transform infrared (FT-IR) spectros-copy was carried out on the alum powder the theobroma oilbeeswax shea butter andmixtures of these bases to ascertainthe compatibility of the drug substance with the differentbases Figures 2ndash6 show the FT-IR spectra of the alumtheobroma oil beeswax shea butter and different combi-nations respectively In developing a rectal suppositorydosage form it is very essential to carry out drug-base in-teraction studies to help eliminate the issues of incompat-ibility and stability and ensure the release of the drug fromthe base used in the formulations

Figure 1 Powdered alum sample produced from bauxite waste inGhana

6 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

)eobroma oil shea butter and beeswax gave identicalspectra )ey showed peaks in the ranges of 292047 cmminus1 to291529 cmminus1 285178 cmminus1 to 284871 cmminus1 174463 cmminus1

to 173547 cmminus1 147065 cmminus1 to 146411 cmminus1117633 cmminus1 to 116112 cmminus1 and 71971 cmminus1 to71871 cmminus1 which corresponds to C-H (CH2) C-H (CH3)stretching vibrations -CO stretching vibrations of acidsand esters [32] -C-H-(CH2CH3) bending vibrations of CH2and CH3 aliphatic groups [33 34] and C-O bond of estersand bending vibrations of a methylene group present [32]respectively Moreover their respective physical mixturesrevealed absorption bands in the ranges of 291733 cmminus1 to291513 cmminus1 286106 cmminus1 to 284871 cmminus1 174400 cmminus1 to173491 cmminus1 147093 cmminus1 to 146331 cmminus1 117565 cmminus1

to 117072 cmminus1 11463 cmminus1 to 11448 cmminus1 and71971 cmminus1 to 71727 cmminus1 Comparative analysis shows thatthere are no significant differences (Pgt 005) in the ab-sorption bands indicating no chemical interaction betweenthe bases and the drug )ere were no major shifts elon-gations broadening widening and shortening of theprominent peaks of the bases Furthermore there were nonew peaks found in the physical mixtures of drug and thebases Comparatively the interaction was independent of thetype of base or mixture of bases

34 Physical Appearance of the Formulated Suppositories)e suppositories prepared were very smooth and torpedo-shaped and had no trapped air when they were cut open Allthe suppositories formulated with shea butter and beeswaxhad a characteristic smell due to the high amount of sheabutter which has a strong characteristic odour and thetheobroma oil-formulated suppositories had a chocolatesmell which is characteristic of the smell of 5eobromacacao )e suppositories were satisfactory in appearanceaccording to British Pharmacopoeia specification [20]

35 Quality Assessment of the Formulated Suppositories)e Pharmacopeia requires weight variation disintegrationand content uniformity tests to be conducted on supposi-tories Table 4 gives the results of the tests conducted

)e suppositories had uniform weight in accordancewith BP specification [24] )e uniform weight predicts a

uniform distribution of the alum in the suppositories andthat there is no variation in the amount of alum in eachsuppository )e uniformity of content test assesses sup-pository-to-suppository and batch-to-batch consistency forproduction technique optimization )e requirements fordrug content are met if the amount of the drug substance ineach of the 10 dosage units as determined by the ContentUniformity method lies within the range of 850 to 1150 ofthe label claim All formulated suppositories were found tobe within acceptable limits [24] )is confirms the unifor-mity of the dose and hence an anticipated uniform thera-peutic response

According to the British Pharmacopoeia [24] disinte-gration of suppositories occurs when the test sample softensor dissolves completely For fatty base suppositories this isexpected to occur within 30minutes All components exceptfor alum (shea butter theobroma oil and beeswax) areoleaginous in nature and soften on exposure to temperatureAll the formulated suppositories passed the disintegrationtest However the disintegration time for the shea butter andbeeswax combination increased with increasing amounts ofbeeswax which is as expected due to the hardening effect ofthe beeswax )is trend was also observed by OladimejiFrancis and Adeyemi [35] when they formulated metroni-dazole suppositories using shea butter and cocoa buttermodified with 20 ww of beeswax Saleem et al [36] alsoobserved that the disintegration time increased when tra-madol hydrochloride suppositories were prepared withcocoa butter modified with 1 ww and 3 ww beeswax

36 In Vitro Drug Release of the Suppositories For suppos-itories the dissolution of medicaments in the rectal fluidprecedes absorption and this can be tested in vitro Disso-lution of drugs is the rate-determining step in the absorptionof drugs and subsequent pharmacological activityAccording to the British Pharmacopoeia [24] the drugrelease from nonmodified dosage forms at time 45 minutesin the dissolution medium should not be less than 70From the result as shown in Figure 7 the suppositoryformulations BS1 BS2 BS3 BS4 BS5 and BT had theunsatisfactory release of the alum (Aw) into the solution attime 45 minutes One of the first requisites for a suppositorybase is that it should remain solid at room temperature butsoften melt or dissolve readily at body temperature so thatthe drug is fully available soon after insertion [9] )e lowrelease could be due to the incorporation of beeswax toimprove upon the melting properties and mechanicalstrength of the shea butter and theobroma oil

Beeswax is highly hydrophobic therefore incorporatingit into the formulation increases the hydrophobicity of thewhole formulation )e increase in the hydrophobic naturedecreased the softening tendency of the bases in the medium(water) and hence affected the release of the drug by trappingthe alum in itself [37] )e presence of beeswax caused adispersion of the suppositories in the dissolution mediumand thus impacted negatively on the release rate Eventhough the release of alum from the suppository was low at45 minutes the release could reach 7114plusmn 430 in 180

Table 3 Displacement values of alum (Aw) in the base

Suppository base Displacement valueBS1 173plusmn 0014BS2 172plusmn 0007BS3 170plusmn 0000BS4 169plusmn 0021BS5 164plusmn 0007BT 176plusmn 0042TH 173plusmn 0028ST1 173plusmn 0014ST2 170plusmn 0007ST3 172plusmn 0000BS beeswax with shea butter BT beeswax with theobroma oil TH the-obroma oil ST shea butter with theobroma oil Values are meanplusmn standarddeviation (n 3)

)e Scientific World Journal 7

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

minutes for the beeswax-theobroma oil )is indicated acontrolled or slow release property of the formulations and ahigh probability for their use as controlled release sup-positories Saleem et al [36] and Oladimeji Francis andAdeyemi [35] observed similar slow release of tramadolhydrochloride and metronidazole respectively from cocoabutter and shea butter modified with different amounts ofbeeswax Saleem et al [36] attributed the slow release oftramadol hydrochloride to high lipophilicity of the base

high water solubility of tramadol hydrochloride non-miscibility of the base with the dissolution media and ab-sence of additives or surface-active agents )e alum is alsohighly soluble in water and was incorporated in a lipophilicbase without any additive and surface-active agent hencesharing the same fate of slow release )e alum release washowever better than that of tramadol hydrochloride )eslow release of the alum from the base was correlated withthe amount of beeswax added

T

T

T

100959085807610190807060541009080706053

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 2 FT-IR spectra of (a) alum (b) theobroma oil and (c) theobroma oil + alum (1 1)

T

T

T

1009590858076101908070605110190807059

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 3 FT-IR spectra of (a) alum (b) shea butter and (c) shea butter + alum (1 1)

T

T

T

101

101

80

60

40

9080706047

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 4 FT-IR spectra of (a) alum (b) beeswax + alum (1 1) and (c) beeswax

8 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

)e release of the alum from the suppository formula-tions TH ST1 ST2 and ST3 at time 45 minutes was7671plusmn 352 8243plusmn 33 7353plusmn 234 and7775plusmn 292 respectively (Figure 8)

)e shea butter and cocoa butter suppositories are li-pophilic suppositories that melt at rectal temperature torelease medicament Due to this their release is greatlyaffected by temperature as their softening time shortens )ealum ldquoAwrdquo is a freely water-soluble drug and will have a hightendency to migrate from a lipophilic base into an aqueous

dissolution medium )e results showed that the supposi-tory formulations without beeswax (TH ST1 ST2 and ST3)could be considered as an immediate release suppositorydosage form [24] )e amount of alum released at 45minutes from the shea butter and cocoa butter combinationswas higher than other drug release studies using similarbases [35ndash40] Some of these studies had the inclusion ofdifferent amounts of Tween 80 as a surfactant )eobromaoil is costly and scarce in our part of the world hence thiscan increase the overall cost of the production of

T

T

T

10095

1019080706056

10190807058

90858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 6 FT-IR spectra of (a) alum (b) beeswax + shea butter + alum (1 1 1) and (c) beeswax + shea butter (1 1)

T

T

T

101908070605210190807057

1009590858076

cmndash14000 3500 3000 2500 2000 1500 1000 500 400

(a)

(b)

(c)

Figure 5 FT-IR spectra of (a) alum (b) shea butter + theobroma oil + alum (1 1 1) and (c) shea butter + theobroma oil (1 1)

Table 4 Quality control evaluation of various suppository formulations

Formulation Weight variation(n 20)

Disintegration time (min) (n 6)(meanplusmn SD) Content of alum in suppositoryplusmn SD () (n 10)

BS1 Pass 621plusmn 009 9797plusmn 0986BS2 Pass 828plusmn 012 9646plusmn 1666BS3 Pass 958plusmn 020 9741plusmn 1097BS4 Pass 1036plusmn 010 9504plusmn 3161BS5 Pass 1469plusmn 033 9441plusmn 3359BT Pass 526plusmn 010 9931plusmn 1446TH Pass 311plusmn 014 9836plusmn 3088ST1 Pass 210plusmn 007 9488plusmn 3112ST2 Pass 256plusmn 017 9974plusmn 2803ST3 Pass 319plusmn 008 9631plusmn 2157BS beeswax with shea butter BT beeswax with theobroma oil TH theobroma oil ST shea butter with theobroma oil SD standard deviation

)e Scientific World Journal 9

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

suppositories of alum Formulation ST3 was chosen to be themost suitable base for the alum since it contained the leastamount of theobroma oil (or more shea butter) and may bethe cheapest to produce )e demand for shea butter wouldboost the economic fortunes of the shea butter industry inGhana

37 Rectoanal Coefficient (RAC) and Histological FindingsApplication of croton oil to the anal region has been found toinduce inflammation and tissue damage that results inhemorrhoid formation in rats [41] Hemorrhoid formationis associated with destruction of the mucus epitheliumnecrosis of the mucus layer infiltration of inflammatorycells and vasodilatation [41 42]

In this work rectoanal coefficient (RAC) also known asldquoorgan to body weight ratiordquo was one of the parametersmeasured to evaluate the severity of hemorrhoids induced inthe rats RAC is a simple means of comparing the extent ofinflammation in the rectoanal tissue [28] As expectedevaluation of rectoanal coefficient presented as columngraphs (Figure 9) revealed that the croton oil (disease)group showed significantly high RAC (203plusmn 007P 00004) when compared to the naıve control

(0852plusmn 002) Also as anticipated the vehicle (bland base)did not have an effect on croton oil-induced hemorrhoids asthe vehicle group showed significantly high RAC(208plusmn 004 Plt 00001) when compared to the naıve andsimilar to that of the croton oil (disease) control )e resultsfurther showed that croton oil-induced hemorrhoid wasresponsive to anti-inflammatory drug treatment as the anti-inflammatory drug diclofenac significantly reduced theRAC to 102plusmn 004 (P 00171) when compared to thevehicle (208plusmn 004) Interestingly the formulated productcaused a significant reduction in the RAC to 102plusmn 003(P 00203) suggesting that it has an ameliorative effect oncroton oil-induced hemorrhoids )ese results althoughpreliminary are very significant as Azeemuddin and col-leagues [28] have used this same animal model to show theefficacy of the herbal formulations in hemorrhoids

)e results obtained from the RAC analysis is furthercorroborated by the histopathology investigation presentedas photomicrographs (Figure 10) Not surprisingly both thedisease control (Figure 10(b)) and vehicle control(Figure 10(c)) showed a very extensive loss of rectoanalintegrity as evidenced by denaturation of the muscularismucosa (ML) submucosa (SM) and lamina propria (LP) ascompared to the naıve (Figure 10(a)) On the other hand

Cum

ulat

ive

dru

g re

leas

e

8070605040302010

00 50 100

Time (min)150 200

BS 1BS 2BS 3

BS 4BS 5BT

Figure 7 A plot of cumulative percentage alum release with time for suppository formulations BS1 BS2 BS3 BS4 BS5 and BT (BSbeeswax + shea butter BT theobroma + beeswax) Error bars represent the standard deviation of six replicates

Cum

ulat

ive

dru

g re

leas

e 120

100

80

60

40

20

0

Time (min)0 50 100 150 200

THST1

ST2ST3

Figure 8 Plot of cumulative percentage release of alum against time for suppository formulations TH ST1 ST2 and ST3 (ST sheabutter + theobroma oil TH theobroma oil) Error bars represent the standard deviation of six replicates

10 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

this damage was less severe in the diclofenac-treated(Figure 10(d)) and alum-treated groups (Figure 10(e))confirming that this model is responsive to anti-inflam-matory drug treatment and that alum (Aw) treatment wasprotective against croton oil-induced hemorrhoids

Diclofenac the standard anti-inflammatory drug used inthis analysis is a nonsteroidal anti-inflammatory drug thatinhibits cyclooxygenase activity to inhibit inflammation )ecurrent work did not investigate the mechanism of action ofalum (Aw) in croton oil-induced hemorrhoids However the

lowastlowastlowast

Rect

oana

l coe

ffici

ent (

RAC)

ns

lowastlowastlowast

00

05

10

15

20

25

Crot

on o

il

Veh

icle

Dic

lofe

nac s

upp

ldquoAw

rdquo (ST

3) su

pp

Naiuml

ve

Croton oil

Figure 9 Effect of various treatments on the rectoanal coefficient in croton oil-induced hemorrhoids in rats Data were expressed asmeanplusmn SEM nsnot significant lowastlowastlowastPlt 0001 when compared to naive and Plt 005 when compared to vehicle using KruskalndashWallisnonparametric one-way ANOVA followed by Dunnrsquos post hoc test (n 5)

(a) (b)

(c) (d)

(e)

Figure 10 Photomicrographs of the naıve control (a) and croton oil-induced inflammation in the rectoanal tissues in rats (bndashe) (a)Histology of the rectoanal tissue of the naıve control group (G1) (b) Histology of the disease control group (G2) (c) Histology of the vehicle(bland base treatment) treatment group (G3) (d) Histology of the diclofenac treatment group (G4) (15mgkg bodyweight diclofenacsuppository delivered ir) (e) Alum ldquoAwrdquo suppository treatment group (100mgkg bodyweight delivered intrarectally (ir)) IG intestinalgland LP lamina propria E epithelium SM submucosa ML muscularis mucosa

)e Scientific World Journal 11

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

anti-inflammatory effects of alum are already known Alum isknown to inhibit inflammation via a number of mechanismssome of which are implicated in croton oil-induced hem-orrhoids )e alum effect includes the inhibition of immunecell functions such as the reduction in lymphocyte infiltrationinhibition of goblet cell proliferation and decrease in dila-tation and congestion of blood vessels [26] )ese effects maytherefore account for the antihemorrhoid effects of the locallyproduced alum suppositories

4 Conclusions

)e alum produced from the bauxite waste from Awaso inGhana conformed to the British Pharmacopoeia specifica-tions and qualifies as an active pharmaceutical ingredient)ere was no interaction between the alum and the basesused as confirmed by the attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy )e combi-nation of shea butter and theobroma oil (3 1) as a baseensured the immediate release of the alum from the sup-pository and passed the pharmacopoeia tests conducted)eproduced alum suppositories had antihemorrhoid proper-ties comparable to diclofenac sodium as evidenced by therectoanal coefficient and the histopathological evaluationsSuppositories containing beeswax showed controlled or slowrelease properties of the formulations and hence could beused as controlled release suppositories )e alum sup-pository was successfully formulated and had the appro-priate therapeutic outcome

Data Availability

)e data used to support the findings of this study are in-cluded in the article and available from the correspondingauthor upon request

Conflicts of Interest

)e authors declare that there are no conflicts of interestregarding the publication of this article

Acknowledgments

)e authors wish to acknowledge the technical staff of theDepartments of Pharmaceutics Pharmacology and Pa-thology of the College of Health Sciences Kwame NkrumahUniversity of Science and Technology Kumasi Ghana

References

[1] R Stefan A W Friedrich K Schwameis M MittlbockG Steiner and A Stift ldquo)e prevalence of hemorrhoids inadultsrdquo International Journal of Colorectal Disease vol 27pp 2015ndash2020 2012

[2] Z Sun and J Migaly ldquoReview of hemorrhoid disease pre-sentation and managementrdquo Clinics in Colon and RectalSurgery vol 29 pp 22ndash29 2016

[3] J F Johanson and A Sonnenberg ldquo)e prevalence of hae-morrhoids and chronic constipationrdquo Gastroenterologyvol 98 pp 380ndash386 1990

[4] Y G Nassa A Danjuma S B Ayuba S A Yahaya B Inusaand I Yakubu ldquoPrevalence and predictors of hemorrhoidsamong commercial motorcyclists in Kaduna state NigeriardquoWorld Journal of Preventive Medicine vol 4 no 1 pp 1ndash42016

[5] P Alonso-Coello E Mills D Heels-Ansdell et al ldquoFiber forthe treatment of haemorrhoids complications a systematicreview and meta-analysisrdquo American Journal of Gastroen-terology vol 101 no 1 pp 181ndash188 2006

[6] D E Beck 5e ASCRS Textbook of Colon and Rectal SurgerySpringer New York NY USA 2nd edition 2011

[7] S Lorenzo-Rivero ldquoHemorrhoids diagnosis and currentmanagementrdquo 5e American Surgeon vol 75 no 8pp 635ndash642 2009

[8] J J Tjandra J J Tan J F Lim C Murray-GreenM L Kennedy and D Z Lubowski ldquoRectogesic (glyceryltrinitrate 02) ointment relieves symptoms of haemorrhoidsassociated with high resting anal canal pressuresrdquo ColorectalDiseases vol 9 no 5 pp 457ndash463 2007

[9] L Allen and H C Ansel Anselrsquos Pharmaceutical DosageForms and Drug Delivery Systems Lippincott Williams ampWilkins Philadelphia PA USA 10th edition 2014

[10] M E Aulton Pharmaceutics the Science of Dosage FormDesign Churchill Livingstone London UK 2nd edition2002

[11] D Jones PharmaceuticsmdashDosage Form and Design Phar-maceutical Press London UK 2008

[12] ldquoAlum by encyclopedia britannica 2014rdquo 2020 httpswwwbrtitannicacomsciencealum

[13] R Mariyam and B Wajeeha ldquoA review on medicinal aspect ofalum in Unani medicine and scientific studiesrdquoWorld Journalof Pharmaceutical Research vol 4 no 6 pp 929ndash940 2015

[14] K M NadKarni Indian Materia Medica Popular PrakashanMumbai India 1982

[15] A M Al-Abbasi ldquo)e benefit of alum in tonsillectomyrdquoGomal Journal of Medical Sciences vol 7 no 2 pp 124ndash1272009

[16] U Romano A Esposito and M C Clerici Chemistry in theProduction of Alum Schellman Tampa FL USA 2001

[17] F Acquah B Mensah and Y Obeng ldquoProduction of alumfrom awaso bauxiterdquo 2019 httphomeattnet7EafricantechGhIEAwaso1htm

[18] R K Etuaful and R Buamah Production of Alum fromBauxite Waste from Awaso Mine College of EngineeringDepartment of Civil engineering Kwame Nkrumah Uni-versity of Science and Technology Kumasi Ghana 2013

[19] httpswwwfdagovfoodfood-additives-petitionsfood-additive-status-list

[20] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2015

[21] A I Vogelrsquos J Mendham R C Denney J D Barnes andM )omas Vogelrsquos Textbook of Quantitative ChemicalAnalysis Prentice-Hall New York NY USA 2000

[22] S J Carter Cooper amp Gunnrsquos Tutorial Pharmacy CBS Pub-lishers amp Distributors Pvt Ltd New Delhi India 6th edition2005

[23] httppharmichblogspotcom201602displacement-valueshtml

[24] British Pharmacopeia Commission British PharmacopeiaHer Majestyrsquos Stationary Office London UK 2017

[25] G L Amidon H Lennernas V P Shah and J R Crison ldquoAtheoretical basis for the biopharmaceutic drug classificationthe correlation of in vitro drug product dissolution and in vivo

12 )e Scientific World Journal

bioavailabilityrdquo Pharmaceutical Research vol 12 pp 413ndash420 1995

[26] A H Baria R P Patel A M Suthar and R B ParmarldquoFormulation development and evaluation of sustained re-lease aceclofenac suppositoryrdquo International Journal ofPharmaceutical Sciences and Drug Research vol 1 no 2pp 71ndash73 2009

[27] R A Dickson T C Fleischer E Ekuadzi and G KomlagaldquoAnti-inflammatory antioxidant and selective antibacterialeffects of Euadenia eminens root barkrdquo African Journal ofTraditional Complementary and Alternative Medicines vol 9pp 271ndash276 2012

[28] M Azeemuddin G L Viswanatha M Rafiq et al ldquoAnimproved experimental model of hemorrhoids in rats eval-uation of anti-hemorrhoidal activity of an herbal formula-tionrdquo ISRN Pharmacology vol 7 pp 1ndash8 2014

[29] A U Birnin-Yauri and A Musa ldquoSynthesis and analysis ofpotassium aluminium sulphate (alum) from waste aluminiumcanrdquo International Journal of Advanced Research in ChemicalScience vol 1 no 8 pp 1ndash6 2014

[30] httpsenwikipediaorgwikipotassium20alum[31] M J Lerma-Garcıa A Gori L Cerretani E F Simo-Alfonso

and M F Caboni ldquoClassification of Pecorino cheeses pro-duced in Italy according to their ripening time andmanufacturing technique using Fourier transform infraredspectroscopyrdquo Journal of Dairy Science vol 93 pp 4490ndash4496 2010

[32] R Karoui and J De Baerdemaeker ldquoA review of the analyticalmethods coupled with chemometric tools for the determi-nation of the quality and identity of dairy productsrdquo FoodChemistry vol 102 pp 621ndash640 2007

[33] L E Rodrıguez-Saona N Koca W J Harper andV B Alvarez ldquoRapid determination of Swiss cheese com-position by Fourier transform infraredattenuated total re-flectance pectroscopyrdquo Journal of Dairy Science vol 89pp 1407ndash1412 2006

[34] A Oladimeji Francis and A Adeyemi ldquoEffects of someinteracting variables on the physical and release properties ofmetronidazole suppositories formulated with modified nat-ural fatty basesrdquo International Journal of ChemTech Researchvol 10 no 9 pp 1046ndash1057 2017

[35] M A Saleem M Taher S Sanuallah et al ldquoFormulation andevaluation of tramadol hydrochloride rectal suppositoriesrdquoIndian Journal of Pharmaceutical Sciences vol 70 no 5pp 640ndash644 2008

[36] F A Oladimeji O D Ogundipe and V O BankoleldquoQuantitative analysis of the effects of drug- base ratio on thephysical and release properties of paracetamol suppositoriesrdquo5e Pharma Innovation Journal vol 6 no 9 pp 190ndash1962017

[37] A Adegoke F A Oladimeji and A O Oyedele ldquoFormulationof metronidazole suppositories with modified cocoa butterand shea butter bases for enhanced stability in tropical en-vironmentrdquo Journal of Pharmaceutical Research Developmentand Practice vol 1 no 1 pp 12ndash24 2016

[38] S Hargoli J Farid S H Azarmi S Ghanbarzadeh andP Zakeri-Milani ldquoPreparation and in vitro evaluation ofnaproxen suppositoriesrdquo Indian Journal of PharmaceuticalScience vol 75 no 2 pp 143ndash148 2013

[39] O Takatori N Shimono K Higaki and T Kimura ldquoEval-uation of sustained release suppositories prepared with fattybase including solid fats with high melting pointsrdquo Inter-national Journal of Pharmaceutics vol 278 no 2 pp 275ndash282 2004

[40] E Gurel S Ustunova B Ergin et al ldquoHerbal haemorrhoidalcream for haemorrhoidsrdquoChina Journal of Physiology vol 56no 5 pp 253ndash262 2013

[41] L Varut ldquoHemorrhoids from basic pathophysiology toclinical managementrdquo World Journal of Gastroenterologyvol 18 no 17 pp 2009ndash2017 2012

[42] O-S Park H-J Kim K-S Kim J-H Cha and Y-B KimldquoAnti- inflammatory effect of alum to experimental paranasalsinusitis of rabbitrdquo 5e Journal of Korean Medicine Oph-thalmology and Otolaryngology and Dermatology vol 19no 1 pp 31ndash42 2006

)e Scientific World Journal 13