Synthesis and characterization of PEGylated derivatives of rosin for sustained drug delivery

REACTIVE

Reactive & Functional Polymers 66 (2006) 1373–1383

www.elsevier.com/locate/react

&FUNCTIONALPOLYMERS

Synthesis and characterization of PEGylated derivatives ofrosin for sustained drug delivery

V.S. Nande *, U.V. Barabde, D.M. Morkhade, A.T. Patil, S.B. Joshi

Department of Pharmaceutical Sciences, Nagpur University Campus, Amravati Road, Nagpur 440 033, Maharashtra, India

Received 24 March 2006; accepted 26 March 2006

Available online 18 May 2006

Abstract

Ester-adduct derivatives of rosin were synthesized by reacting rosin with polyethylene glycol 200 (PEG 200) and maleicanhydride (MA) at elevated temperature. The different concentrations of PEG 200 (7.5%, 15% and 25% w/w of rosin) wereused with fixed concentration of MA (7.5%) to obtain derivatives. These derivatives were evaluated for acid number, glasstransition temperature (Tg), solubility, FT-IR spectroscopy, molecular weight (Mw) and polydispersity. Water vaportransmission rate (WVTR) of free and applied (on tablets) derivative films was investigated. The PEG 200 concentrationshowed proportional increase in the molecular weight and reciprocal relation with the acid number and Tg of the rosinderivatives. The derivatives were soluble in organic solvents; aqueous solubility was pH dependent. The contact anglestudy revealed higher wettability of derivatives compared to rosin films. WVTR of derivative-coated tablets was muchlower than for the free films. Further, the derivatives were investigated as matrix former in tablets and pellets using dic-lofenac sodium (sparingly soluble in water) and propranolol hydrochloride (soluble in water) as model drugs. While therelease of diclofenac sodium was retarded for 8 h in both dosage forms, propranolol hydrochloride was completely releasedwithin 2 h. The results support applications of these rosin derivatives in different drug delivery systems.� 2006 Elsevier B.V. All rights reserved.

Keywords: Rosin derivatives; Polyethylene glycol; Film properties; Matrix tablets; Pellets

1. Introduction

For more than three decades, the delivery of bio-active agents from polymeric materials has attractedconsiderable attention. Polymers have been used fordifferent purposes depending upon their physico-chemical properties. One of the most sought afterarea in polymer sciences for pharmaceutical use isthat of natural polymers. Being products of living

1381-5148/$ - see front matter � 2006 Elsevier B.V. All rights reserved

doi:10.1016/j.reactfunctpolym.2006.03.021

* Corresponding author. Tel.: +91 712 5626866.E-mail address: [email protected] (V.S. Nande).

organisms, readily available, relatively less expen-sive and capable of a multitude of chemical modifi-cations, they remain attractive even after the adventof synthetic polymers. These polymers also offerbetter drug efficacy, reduced toxicity and improvedpatient compliance and therefore are finding moreinterest in drug delivery [1].

Rosin or colophony is a clear, pale yellow to darkamber, thermoplastic solid resin obtained from thetrees of Pinus species (Family – Pinaceae). The majorcomponents of rosin include resin acids representedby general formula C20H30O2 that are present as free

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1374 V.S. Nande et al. / Reactive & Functional Polymers 66 (2006) 1373–1383

acids or dimmers or as anhydrides [2]. They aremonocarboxylic acids of alkylated hydrophenanth-rene; abietic acid constitutes the principal resin acid[3,4]. The oral toxicity studies on animals haveproved rosin to be practically non-toxic. The mini-mum dose that killed 50% of animals tested (LD50)showed an increasing trend with derivatization ofrosin; the maleic anhydride-pentaeryhtritol ester ofrosin being four times safer than the parent materialin guinea pigs [5].

Rosin derivatives have been investigated for theirusefulness as pharmaceutical aid in film coating [6],matrix formation [7] and microencapsulation [8].Glycerol derivatives of rosin have been reported tobe biodegradable [9]. The exact course of reactionand nature of the final product was difficult to deter-mine in view of their complex composition. A sim-plified composition of rosin derivative with onlythree components in the reaction has been recentlyreported [10]; the derivative exhibited good filmforming ability and was biodegradable.

Polyethylene glycol (PEG) or poly (ethyleneoxide) represents water-soluble mono hydroxy alco-hols that have been employed in many pharmaceu-tical applications. These are water-soluble polymersused as base in ointments and suppositories, as plas-ticizer in film coating, as auxiliary emulsifiers, etc.[11]. The technique of attaching PEG to any drug,peptide, polymer or any chemical moiety has beentermed as ‘PEGylation’. The biological applicationsof PEG and its conjugates with drugs, proteins orother biomolecules have been well documented[12]. Recently, long circulating drug delivery sys-tems of PEG conjugates has gained more attentionowing to their longer biological half lives, betteracceptability by body tissues and improved abilityto deliver drugs to the intended tissues [13–15]. Ina recent study, a hydrophobic polymer polylactide(PLA) was co-polymerized with PEG to increasethe hydrophilic segments of the resulting moiety.The microcapsules so obtained were more perme-able to water than PLA [16].

The two reactive sites of resin acids – carboxylgroup and conjugated double bond – were utilizedto synthesize the present ester-adduct derivatives.A primary alcohol – PEG 200 – was reacted withan acid – resin acid – to get an ester. Maleic anhy-dride was then reacted with this product to formester-adduct derivative of rosin. While the concen-tration of PEG 200 was varied in the derivativepreparation, that of maleic anhydride was kept con-stant. The effect of these components on the differ-

ent physico-chemical properties of derivatives wascompared against rosin. These derivatives were alsoevaluated for their usefulness as drug release-retard-ing property in tablets and pellets.

2. Experimental

2.1. Materials

Rosin (N grade) was purchased from ShabbirChemicals, Nagpur, India. Polyethylene glycol 200(PEG 200) and maleic anhydride (MA) were pur-chased from Qualigens, Mumbai, India, and S.D.Fine Chemicals, Mumbai, India, respectively. Pro-pranolol hydrochloride and diclofenac sodium werereceived as gift samples from Sun PharmaceuticalsIndustries Limited, Vadodara, India and Zim Labo-ratories, Nagpur, India, respectively. All the otherchemicals used were of analytical grade and wereused as received.

2.2. Synthesis and evaluation of derivatives

Rosin (N grade) was placed in a glass reactor andheated to 220–240 �C on a sand bath. PEG 200 wasmixed with this molten mass using a glass stirrer.The temperature of the mixture was maintained at240–260 �C till the completion of reaction. Zinc dust(0.5%) was added as catalyst. Acid number of themixture at every 1-h interval indicated fate of reac-tion and the insignificant difference between the twosuccessive acid numbers confirmed its completion.Further, the melt was allowed to cool to 140–160 �C. MA was added to this melt and the reactionwas continued for 1 h. The molten mass was pouredon steel plates, allowed to solidify, powdered,washed thoroughly with water and air-dried. Toconfirm the changes in material characteristics,rosin was treated under similar conditions withoutaddition of any reactants and treated as reference.

Softening and melting points of derivatives weredetermined by capillary method. Formation ofnewer functional groups in the derivatives was con-firmed using FT-IR spectroscopy (Shimadzu).Molecular weights and polydispersity were esti-mated using gel permeation chromatography (Per-kin–Elmer) with a differential refractometer (LaChrom Detector L-7490). Differential scanning cal-orimeter (DSC, Mettler-Toledo) was employed todetermine glass transition temperature (Tg). Thephysical form of the derivatives was determined byX-ray diffraction (XRD) technique.

V.S. Nande et al. / Reactive & Functional Polymers 66 (2006) 1373–1383 1375

2.3. Solubility of derivatives

Solubility of the derivatives in different buffers andorganic solvents was gravimetrically determined.Approximately 5 g derivative was placed in 10 mlmedia for testing in different test tubes, agitated inwater bath shaker for 24 h at 25 ± 0.5 �C and filtered.One milliliter of the filtrate was pipetted into pre-weighed porcelain dish, dried at 40 �C and weighed.The difference in weights gives solubility per mL. Var-ious buffers of pH 1.2, 5.0, 6.8, 7.5 and 10.0, and theorganic solvents acetone, isopropyl alcohol, dichlo-romethane and chloroform were used for this study.

2.4. Preparation of free films

A 30% w/w solution of derivative in acetone wasused for casting free films by solvent evaporationtechnique on mercury substrate [17]. The derivativesolution was allowed to air-dry.

2.5. Angle of contacts of films

Wettability of rosin and its derivative films wasstudied by measuring their contact angles withwater drop. Glass slides were dipped in their solu-tions and dried at 40 �C for 24 h to form uniformfilms. These slides were mounted on a horizontalplatform; water drops (100 ll) were carefully placedonto them from a distance of approx. 5 mm. Thecontact angles of water drops with the films weremeasured using a protractor and a magnifying glassat 10 min interval up to 30 min. This study was fur-ther extended with two physiological pH of the gas-trointestinal tract using sodium chloride buffer pH1.2 and phosphate buffer pH 6.8.

2.6. Water vapor transmission rate (WVTR)

Thickness of free films of derivatives was deter-mined using a micrometer screw gauge. Films ofpredetermined thickness were fixed on mouth ofthe glass vials using silicon wax and aluminum seal.These vials were containing fused calcium chlorideas desiccant. These vials were kept in desiccatorsmaintained at relative humidity conditions of 43%and 75% at 25 ± 0.5 �C for 24 h. The weight gainsof vials indicated the amount of water vapor trans-mitted through the films. Water vapor transmissionrate was calculated by using the formula [18]:

Q ¼ W � L=S

where Q is the water vapor transmission rate ing cm/cm2 per 24 h; W is the weight in gram of watertransmitted in 24 h; L is the film thickness in cm; S

is the surface area of exposure in cm2.This study was extrapolated to tablets containing

highly water-soluble material. Tablets of potassiumnitrate were prepared by wet granulation methodusing povidone K-30 (2% w/v aqueous solution)as binder. These tablets were coated with the deriv-atives for weight gain of 3% and 5% w/w using aspray gun and a tablet coating assembly. The aver-age total surface area of the coated tablets wasdetermined. The tablets were subjected to similarrelative humidity conditions as used for free films.The WVTR was calculated using the formula asmentioned earlier.

2.7. Derivatives as release retarding matrix formers

The drug release-retarding matrix forming prop-erty of the derivatives was investigated. Diclofenacsodium (sparingly soluble in water) and propranololhydrochloride (soluble in water) were used as modeldrugs. Wet granulation technique was used to pre-pare the tablets using derivative solution (in isopro-pyl alcohol) as binder and matrix former. Thederivatives were used in concentrations of 20% and30% w/w of tablet weight. The granules were driedat 40 �C for 12 h. The release of drug from the tabletswas studied in buffer pH 1.2 for first 2 h followed bybuffer pH 6.8 for 6 h using USP dissolution appara-tus Type II (paddle) at 75 rpm at 37 ± 0.5 �C.

Pellets were prepared using 20% w/w derivativesby extrusion-spheronization method. Granulationwas carried out using isopropyl alcohol and water.The wet mass was extruded through 1.5 mm screenand spheronized at 900 rpm for 5 min and dried at40 �C for 12 h. The release of drug from pellets wasstudied in buffer pH 1.2 for 1 h followed by bufferpH 6.8 for further 7 h using USP dissolution appara-tus Type I (basket) at 75 rpm at 37 ± 0.5 �C. Cumu-lative drug release from the matrices was determinedspectrophotometrically at 276 nm and 290 nm fordiclofenac sodium and propranolol hydrochloride,respectively.

3. Results and discussion

3.1. Synthesis and characterization of derivatives

The composition of the derivatives is given inTable 1. The reaction of an acid with an alcohol

Table 1Composition of derivatives

Derivative Poly (ethylene glycol) 200a Maleic anhydridea

PD-1 7.5% w/w 7.5% w/wPD-2 15.0% w/w 7.5% w/wPD-3 25.0% w/w 7.5% w/w

a Calculated with respect to rosin.


to form ester and water is reversible that leads toformation of impure products. Products with highester yield can be obtained either by using catalystsor by use of one of the reacting components in largeexcess or by removal of water. In view of this, it maybe noted that the reaction temperature in the cur-rent scheme spontaneously removed any water mol-ecule and the reaction continued till the completeconversion of PEG 200 into esters of resin acid.Addition of zinc granules significantly increased

Fig. 1. Reaction scheme of derivative synthesis

Table 2Physico-chemical properties of rosin and the derivatives

Appearance Rosin PD

Pale yellow solid Ye

Softening point (�C) 80–85 60Melting point (�C) 110–115 85Molecular weighta 380 (1.13) 55Glass transition temperature (Tg) �C <30 42Acid number (mg of KOH) 169.54 12pH of 1% suspension 5.81 5.9

a Values in parenthesis indicate Polydispersity (Mw/Mn).

the reaction rate. These esters were soft at roomtemperature and difficult to handle. However, addi-tion of maleic anhydride improved the physicalcharacteristics of the products. The sequence ofreaction taking abietic as model component is givenin Fig. 1.

The physicochemical properties of rosin and thederivatives are illustrated in Table 2. In the presentstudy, the color of the derivatives changed from yel-low to reddish brown with increase in PEG 200 con-centration. The concentration of PEG 200 in thereaction mixture proportionally converted resinacids into esters and exhibited reciprocal relation-ship with the acid number. The acid number forPD-1 as highest and for PD-3 as lowest was appar-ent. As the concentration of PEG 200 in the reac-tant mixture increases, more of the resin acids areconverted into PEG ester of higher molecular

taking abietic acid as model compound.

-1 PD-2 PD-3

llow solid Yellowish red solid Reddish brown solid

–65 50–55 45–50–90 75–80 60–651 (1.30) 660 (1.39) 820 (1.40).42 38.10 26.740.93 88.19 57.710 6.02 6.12


weights. Therefore the average molecular weight ofthe derivatives is coincident with the concentrationof PEG 200. Polydispersity values of all derivativesnearer to one indicated uniformity of the reactionproduct.

The FT-IR spectra of the derivatives are given inFig. 2. The spectra of derivatives were comparedagainst that of rosin. In the IR spectra of rosin,

Fig. 2. Infrared spectrum of rosin a

C@O stretching at 1724 cm�1 and O–H stretchingat 3568 cm�1 indicated the presence of carboxylicacid. However, in addition to these two peaks, theIR spectra of all the derivatives show C@O stretch-ing at 1740 cm�1 suggesting formation of ester [19].An additional stretching at 1780 cm�1 also indi-cated the presence of cyclic anhydride in the struc-ture. These results suggested PEG 200 and MA

nd the synthesized derivatives.


react with rosin acids to form ester-adduct product.The observation that the average molecular weightof the derivatives was coincident with the concentra-tion of PEG 200 is noteworthy.

No significant changes were observed in thematerial characteristic when rosin was treated undersimilar conditions. While the color of the productchanged from pale yellow to reddish brown, the acidnumber and molecular weight remained the same;IR spectra was superimposable with untreatedrosin. Significantly, the film forming property oftreated rosin was lost – no film could be formedusing any solvent or solvent system.

The Tg values of derivatives displayed reciprocalrelation with the concentration of PEG 200. Theliquid nature of PEG 200 at room temperature mightbe responsible for the decrease in Tg values of thederivatives. From highest to lowest Tg values ofPD-1 to PD-3 is in accordance with our assump-tions. The minimum film forming temperature ofthe derivatives proportionately decreased with theTg values indicating the possibility of film coatingat room temperature. Since the X-ray diffractogramof all derivatives did not show any specific refractionpattern, their amorphous form may be suggested(data not shown). The pH of 1% suspension of deriv-atives shows an increasing trend with the PEG con-centration in the derivatives. The conversion ofcarboxylic acid group into ester might be the reasonfor this change.

3.2. Solubility of derivatives

Solubility of the derivatives at different pH isshown in Table 3. Solubility of all the derivativesincreased with an increase in the pH of media.The solubility at pH 5.0 and pH 10.0 was 6- and12-folds higher than that at pH 1.2, respectively.This might be the result of formation of salts ofresin acids at higher pH. This pH-dependent solu-bility of derivatives can be used in controlled release

Table 3Solubility of rosin and the derivatives in different buffer media

Buffer media Solubility (mg/mL)

Rosin PD-1

pH 1.2 2.06 ± 0.45 3.2 ± 0pH 5.0 17.10 ± 2.30 17.83 ± 2pH 6.8 30.53 ± 1.09 29.46 ± 0pH 7.5 35.66 ± 3.00 33.43 ± 1pH 10.0 37.50 ± 1.90 38.16 ± 5

of drugs from tablets and pellets. However it wasnoteworthy that the solubility of rosin and its deriv-atives was comparable at different pH. All the deriv-atives were soluble in the organic solvents used inthe present study.

3.3. Morphology of free films

In the present study ‘internal plasticization’ of afilm forming material (rosin) was carried out byreacting it with a plasticizer – PEG 200. SEM ofthe surface and section of free film of the derivativesare shown in Fig. 3. Surfaces of all the derivativefilms were smooth and continuous without anycracks or pinholes. Although, the bulks of PD-1and PD-2 films were free from pinholes, the bulkof PD-3 film was porous. This porous film was weakand less resistant to moisture permeation. In similarstudy when PEG was used as external plasticizer,the increase in molecular weight resulted in increasein the size and number of pores in the cellulose ace-tate films [20]. In the present study, the increase inconcentration of PEG 200 to 25% has resulted information of pores.

3.4. Angle of contact

In the present study, contact angle of water dropwas used as a measure of wettability of the deriva-tive films. A lower contact angle at the solid–liquidinterface means lesser surface tension and therebymore wetting [21]. Angle of contact of water dropwith derivative films as a function of time is shownFig. 4. The angle of contact of water with rosin filmwas higher than the derivative films. The increase inPEG 200 concentration gradually decreased thecontact angle. This decrease in the contact anglemight be due to formation of more hydrophilicdomains in the derivative structure. Lower angleof contact of water with substrate indicates the pres-ence of dominant polar forces at the surface and

PD-2 PD-3

.40 3.40 ± 0.20 2.80 ± 0.45

.36 20.83 ± 0.55 19.93 ± 1.68

.15 28.36 ± 4.53 28.73 ± 2.87

.51 32.00 ± 1.38 32.13 ± 2.43

.20 37.20 ± 1.77 39.66 ± 4.96

Fig. 3. Scanning electron micrographs of surface of free films of PD-1, PD-2 and PD-3 (a), (c) and (e) and their bulk (b), (d) and (f),respectively.


hence higher wettability [22]. The wettability offilms increased from PD-1 to PD-3. Data pertainingto the solubility and contact angle suggests that thederivatives become more hydrophilic as the concen-tration of PEG 200 increases.

Contact angles of buffers of pH 1.2 and 6.8 withthe derivative films are shown in Fig. 5. No signifi-cant change in the wetting behavior of films wasencountered which is indicative of the pH indepen-dent wettability.

Fig. 4. Angle of contact of water droplet with derivative filmswith respect to time.

Fig. 5. Angle of contact of (a) buffer pH 1.2 and (b) buffer pH 6.8with derivative films.

Table 4Water vapor transmission rate of free films of derivatives

Derivatives Filmthickness(lm)

Exposedsurfacearea (cm2)

WVTR (g cm/cm2 24 h) · 10�5

PD-1 210 ± 9 1.538 ± 0.008 12.86 ± 0.026PD-2 190 ± 9 1.538 ± 0.008 18.91 ± 0.019PD-3 175 ± 8 1.538 ± 0.008 32.39 ± 0.020


3.5. Water vapor transmission rate (WVTR)

Water vapor transmission rate can give usefulinsight into the porosity and hydrophilic/hydro-phobic character of film. If the films are porous,more void spaces are available in the films throughwhich the water vapors can pass. A higher WVTRalso indicates the presence of more hydrophilicdomains in film structure [23]. The WVTR of freefilm of the derivatives is represented in Table 4.The number of hydrophilic domains increases withthe concentration of PEG 200 in the derivatives,which is reflected by the WVTR. PD-1 with lowestand PD-3 with highest PEG 200 concentration hasWVTR from least to maximum at 43% and 75%RH. However, the WVTR of all the films werehigh at 75% than at 43% RH and a high differencein RH across the films may be an underlying rea-son for this effect.

The studies on the WVTR of the derivativecoated tablets at different humidity conditions sub-stantially supports effects of components of tabletcore on vapor permeability. The WVTR of thederivative coated tablets is enumerated in Table 5.The WVTR of derivative-coated tablets was much

Table 5Water vapor transmission rate (WVTR) of films on coated tablets of p

Derivatives Exposed tabletsurface area (cm2)

Coating level

PD-1 3.138 ± 0.015 3%PD-2 3.138 ± 0.015 3%PD-3 3.138 ± 0.015 3%PD-1 3.138 ± 0.017 5%PD-2 3.138 ± 0.017 5%PD-3 3.138 ± 0.017 5%

lower than for corresponding free films under simi-lar conditions; the effect may be attributed to thewater vapor gradient across the film [24].

otassium nitrate

Film thickness (lm) WVTR (g cm/cm2 .24 h) · 10�7

70 ± 0.2 6.359 ± 0.01570 ± 0.4 9.121 ± 0.02080 ± 0.2 11.010 ± 0.009

110 ± 0.1 0.655 ± 0.012100 ± 0.2 0.718 ± 0.013120 ± 0.2 0.963 ± 0.017

Fig. 6. Dissolution profile of (a) diclofenac sodium and (b)propranolol hydrochloride from matrix tablets.

Fig. 7. Dissolution profile of diclofenac sodium from (20% w/w)matrix pellets.


At 43% RH, transmission of water vapor wasnot noticed, thus suggests waterproofing ability ofthe films. However at 75% RH, the WVTR wasinversely proportional to the film thickness. TheWVTR of all the derivatives showed decrease from3% to 5% coating. Increase in degree of coatingreduces the available void spaces between the deriv-ative strands thereby restricting the transfer ofmoisture. As with the free films, the WVTR washighest for PD-3 coating and lowest for PD-1.Taken together, a very low WVTR of the deriva-tive-coated tablets suggests the possible utility ofpresent derivatives as moisture-protective coatingmaterial.

3.6. Derivatives as drug release-retarding agents

Granulation of particulate mixture using a poly-mer solution results in coating of the particles withthe polymer; thickness of this coat depends uponthe concentration of the polymer [25]. In the presentstudy, the derivative solution was used to form theprotective coat around the particles during the gran-ulation of drug–excipient mixture. The drug has tocross this barrier coat in order to release in the disso-lution media. The dissolution profile of diclofenacsodium and propranolol hydrochloride from matrixtablets is described in Fig. 6. An increase in the deriv-ative concentration resulted in reduction in releaserate of both the drugs. Moreover, the drug releaserate was increasing from PD-1 to PD-3, which is inagreement with the observation that the presenceof more resin acid–PEG esters makes the derivativesricher in hydrophilic domains. Diclofenac sodiumtablets have sustained the release up to 8 h while pro-pranolol hydrochloride tablets showed completerelease within 3 h. This difference in the release pro-file could be attributed to relative solubility of drugin the derivative matrices. Comparatively high lipo-philicity of diclofenac sodium than propranololhydrochloride can be expected from their octanol/water partition coefficient of 13.4 and 3.65, respec-tively. Thus, higher relative solubility of diclofenacsodium than propranolol hydrochloride in thehydrophobic derivative matrices may be predicted.This eventually releases propranolol hydrochlorideat higher rate than diclofenac sodium.

Propranolol hydrochloride pellets immediatelyreleased the entire drug owing to incomplete coatingby the derivatives. Release of diclofenac sodiumfrom pellets showed reversal of trend obtained withmatrix tablets; higher to lower release rate from

PD-1 to PD-3 derivatives was observed as seen inFig. 7. The pellets became more spherical with theincrease in PEG 200 concentration in derivatives(Fig. 8). The spherocity index (ratio of minimumdiameter to maximum diameter) of diclofenacsodium matrix pellets show increasing trend with

Fig. 8. Photographs of matrix pellets (20%w/w) of (a) PD-1, (b)PD-2 and (c) PD-3.

Table 6Physical properties of diclofenac sodium matrix pellets

Derivatives No. of pelletsin 100 mg

Mean pellet diame(mm)

PD-1 23 ± 2.1 1.730 ± 0.013PD-2 18 ± 1.5 1.933 ± 0.012PD-3 15 ± 1.5 2.073 ± 0.009


the PEG 200 concentration (Table 6). The sphericalpellets give least surface area exposure to the exter-nal media. The release rate decreases in proportionwith the exposed surface area. These results indicatethat not only the solubility of coating material butalso the geometry and technique of manufacturingof the dosage form governs drug release.

4. Conclusions

Ester-adduct derivatives of rosin using PEG 200and MA were prepared. The added amounts ofPEG 200 and MA reacted completely with rosin.The increase in the concentration of PEG 200 inthe derivatives makes them more hydrophilic thanthe parent moiety of rosin. This increase in hydro-philic character was demonstrated by reduction ofangle of contact with water and increased WVTRthrough the films at different RH conditions. Thesederivatives can also be used as moisture barriers fortablets containing hygroscopic material. Thesederivatives may suitably be used in preparing matrixtablets and pellets for sustained release of drugs.The concentration of derivative required for sus-taining the release of propranolol hydrochloride(water-soluble drug) from both the dosage formswas more than for diclofenac sodium, a drug spar-ingly soluble in water.

With increase in the concentration of PEG 200 inthe derivatives the spherocity of pellets improvedwhile retarding the drug release. The present resultssupport other possible applications of these deriva-tives in different drug delivery systems.

Acknowledgements

We express our sincere thanks to Indian Instituteof Technology, Mumbai, India, for GPC facility, toNational Institute for Pharmaceutical Educationand Research, Chandigarh, India, for DSC facilityand to All India Institute of Medical Sciences,New Delhi, India, for providing SEM facility. We

ter Spherocity Total exposed surfacearea (cm2)

0.649 ± 0.006 8.645 ± 0.0110.702 ± 0.009 8.445 ± 0.0230.898 ± 0.002 8.072 ± 0.017


are also sincerely thankful to Mr. Amul Sakharkarfor helping us in preparing this manuscript.

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Synthesis and characterization of PEGylated derivatives of rosin for sustained drug delivery

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