S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers… 1111

Research Paper Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers on the Release Rate and In Vitro Evaluation

S.K. Singh.1*, S.B. Bothara2, S. Singh3, R. Patel4 and R. Dodia5

1Shree H.N.Shukla Inst. of Pharmaceutical Education and Research, Rajkot, India. 2Shri GM BILAKHIA College of Pharmacy ROFEL, Vapi, India. 3C.P.S. Mahuda college of Pharmaceiutical sciences, Bhermpur, India 4Shree Leuva Patel Trust Pharmacy Mahila College, Amreli, India 5Shree Laxminarayandev College of pharmacy, Bharuch, India

ABSTRACT: Extending the residence time of a dosage form at a particular site and controlling the release of drug from the dosage form are useful especially for achieving controlled plasma level of the drug as well as improving bioavailability. The objective of this study was to extend the GI residence time of the dosage form and control the release of Tramadol HCl using mucoadhesive tablet to achieve controlled plasma level of the drug which is especially useful for 12 hrs. Matrix tablets of Tramadol HCl were formulated using different mucoadhesive polymers namely guar gum, xanthan gum and Methocel (HPMC K15M and HPMC K100M). Formulations were evaluated for preformulation parameters, in vitro drug release profile and release kinetics. The formulations were found to have good preformulation characteristics. FTIR spectroscopy indicated the absence of any significant chemical interaction within dug and excipients. The release mechanism of Tramadol HCl from matrix tablets indicated anomalous (non-Fickian) transport mechanism and followed zero order kinetics. The retention time of the mucoadhesive tablet on the mucous membrane were investigated to develop a bioadhesive polymer-based controlled release delivery system and to evaluate the performance of such a delivery devices. The combination of HPMC K15: HPMC K100: Xanthan gum (1:2:1) and HPMC K 100: Xanthan gum (2:2) showed a greater bioadhesive strength as compared to single gum and other hydrophilic polymer combination tablet. The stability studies were performed on optimized formulation as per ICH guideline, result showed that there was no significant change in physical characteristic, adhesive strength and In vitro release.

KEY WORDS: Xanthan gum; Methocel; Tramadol HCl; bioadhesive force

Introduction Oral administration is the most convenient, widely utilized, and preferred route of drug delivery for systemic action. However, when administered orally, many therapeutic agents are subjected to extensive presystemic elimination by gastrointestinal degradation or first pass hepatic metabolism (Gupta et al., 1990, Madsen et al., 1998), as a result of which low systemic bioavailability and shorter duration of therapeutic activity or formation of inactive or toxic metabolites have been reported (Jay et al., 2002, Jimenez et al., 1993). Further, the quick passage of dosage

forms through the absorptive segment of GIT often leads to unutilized drug, particularly in case of extended delivery of narrow absorption window drugs (Akiyama et al., 1999). Much attention has been focused, recently on targeting a drug delivery system to a particular region of the body for extended period of drug release, not only for local targeting of drugs but also for the better control of systemic delivery. The concept of mucoadhesion was introduced into controlled drug delivery in the early 1980s. Mucoadhesives are synthetic or natural polymers, which interact with the mucus layer covering the mucosal epithelial surface and mucin constituting a major part of the mucus. Drug delivery using mucoadhesive dosage form via transmucosal route, bypasses hepato-gastrointestinal

International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 3 • Issue 3 • October - December 2010

* For correspondence: S.K. Singh,

Tel: 02792232323; Mob: 09974756126

E-mail: roshan.cg@gmail.com

1111

1112 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 3 • October-December 2010 first pass elimination associated with oral administration, thereby increases the bioavailability and produces longer therapeutic effect (Harris et al., 1989, Smart et al., 1984).Tramadol HCl and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. The analgesic properties of Tramadol HCl can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. Due to its short biological half the recommended oral dosage is 50-100 mg every four to six hours with a maximum dosage of 400 mg/day (Sean C, 2002, Louis S, 1996). Due to twice to thrice day’s dose the aim of the present cram was to develop, characterize and evaluate mucoadhesive tablet of Tramadol HCl using some synthetic and natural hydrophilic excipient for prolonged gastrointestinal absorption.

Experimental Methods

Materials

Tramadol Hydrochloride were procured from Intas Pharmaceutical Ltd., Ahmedabad, Hydroxy Propyl Methyl cellulose K100M, Hydroxy Propyl Methyl cellulose K15M were procured from Colorcon Asia Pvt. Ltd., Lactose, Microcrystalline cellulose (Avicel pH 102) and Guar gum were procured from Signet Chemical Corp, PVP K 30 were procured from Nice Chemicals Laboratory, Magnesium Stearate and Talc from Loba Chemical. All the chemicals and other reagents used in the study were of AR grade.

Formulation and Optimization of Excipient

Sustained release mucoadhesive oral matrix tablets containing Tramadol HCl were prepared by wet granulation technique using variable concentrations of HPMC K15M, HPMC K100M, Xanthan gum, Guar gum. In all case, the amount of the active ingredient is 100mg. All the ingredients except Avicel pH 102, magnesium stearate and talc were blended in blender uniformly. Granulation was done with sufficient binding solution of PVP K30 and isopropyl alcohol. The lubricated granules were compressed into tablet using 9 mm standard concave punch with 10 station single rotary Clit (Jemkay) machine and keeping average weight 240 mg. All Tramadol HCl loaded matrix tablet were stored in airtight container at room temperature for further study. Tablet of batch F1–F3, F4–F6, F7–F9 and F10–F12 contain only single

mucoadhesive polymer in different concentration, Batch F13–F15 contain combination of two mucoadhesive polymer having drug:gum ratio (4:2:2) and Batch F16 contain combination of various mucoadhesive polymer having drug:gum ratio (4:1:2:1). Compositions of various formulations are shown in (Table 1).

Interference Study

This study has been done to check whether there is any compatibility related problems are associated with drug and excipients used for the formulation of tablet. The drug and excipients must be compatible with one another to produce a product that is stable, efficacious, attractive and easy to administer and safe. If the excipients are new and not been used in formulations containing the active substance, the compatibility studies are of paramount importance. The IR spectral analysis of a drug and other excipients were taken using Press pellet technique (using KBr). The IR spectra’s were determined by using Jasco FTIR-410 (Willard et al., 1988, Sharma 2009, Beckett et al., 2004, Tayed 2005).

Evaluation of the mucoadhesive tablet

All the mucoadhesive tablets prepared were evaluated for the following official parameters: Hardness, Friability (Gilbert S et al., 1990), Weight variation, Thickness and drug content (USP 2008) as per official procedures. The values of all the evaluation parameters are shown in (Table 2).

Swelling Index

Swelling index were determined for each formulation batch, one tablet was weighed and placed in a beaker containing 200 ml of buffer media. After each interval the tablet was removed from beaker and weighed again up to 8 hours. The swelling index was calculated using following formula (Noha Adel naffee et. al., 2004, Lalla JK et. Al., 2002, Juan Manuel Llabot et. al., 2002, Baumgartner S et.al., 2000). Results are summarized in (Table 3) (Figs. 1 and 2).

Swelling Index (S.I.) = (Wt – Wo)/Wo

Where, S.I. = Swelling index

Wt = Weight of tablet at time t

Wo = Weight of tablet before placing in the beaker

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F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

F12

F13

F14

F15

F16

Tram

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HC

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1113

1114 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 3 • October-December 2010

Table 2 Physical Properties of Tablets of Batch F1 to F16.

Batch no.

Weight Variation (mg)

Hardness (kg/cm2)

Thickness (mm)

Friability (%)

Drug content uniformity (mg)

F1 240.7±5.02 6.7±0.252 3.03±0.11 0.55 98.94

F2 240.5±4.00 6.6±0.289 2.80±0.05 0.58 99.10

F3 239.6±3.99 6.4±0.462 2.76±0.05 0.53 98.92

F4 239.4±3.77 7.1±0.361 2.70±0.15 0.39 98.72

F5 240.3±3.01 6.6±0.173 2.66±0.05 0.41 98.19

F6 240.3±2.72 7.4±0.551 2.93±0.15 0.48 98.92

F7 240.1±2.17 6.4±0.436 2.55±0.08 0.61 97.10

F8 240.2±2.29 6.9±0.306 2.62±0.05 0.72 99.28

F9 239.8±2.05 7.1±0.458 2.53±0.052 0.67 98.30

F10 240.1±2.47 6.6±0.173 2.81±0.076 0.48 97.46

F11 240.0±2.11 6.6±0.208 2.76±0.115 0.39 98.19

F12 241.0±2.55 6.7±0.208 2.83±0..064 0.47 98.82

F13 240.1±2.13 6.7±0.666 2.53±0.052 0.54 97.30

F14 241.1±2.57 6.4±0.603 2.81±0.076 0.56 97.46

F15 240.5±2.23 7.1±0.208 2.76±0.115 0.44 99.19

F16 240.3±2.25 7.0±0.200 2.83±0..064 0.38 99.82

Each reading is an average of three determinations (Avg.± S.D)

Table 3 Swelling Index of Tablets of Batch F1 to F16

Time (hrs) Batch no. 0 1 2 3 4 5 6 7 8

F1 0 0.624 0.852 1.041 1.166 1.248 1.250 -- --

F2 0 0.558 0.862 1.045 1.186 1.065 1.024 -- --

F3 0 0.672 0.918 1.122 1.245 1.327 1.347 1.306 --

F4 0 0.616 0.950 1.116 1.241 1.324 1.344 1.386 --

F5 0 0.120 0.399 0.605 0.852 0.934 1.140 1.181 1.201

F6 0 0.126 0.224 0.477 0.646 0.857 0.983 1.025 1.152

F7 0 0.204 0.532 0.660 0.830 0.915 1.000 1.043 1.085

F8 0 0.259 0.570 0.674 0.736 0.860 0.901 0.942 0.983

F9 0 0.561 0.880 1.160 1.380 1.460 1.480 1.520 1.540

F10 0 0.688 0.934 1.016 1.119 1.140 1.222 1.305 1.322

F11 0 0.599 0.803 0.926 1.008 1.131 1.172 1.254 1.295

F12 0 0.674 0.922 1.150 1.138 1.145 1.276 1.321 1.333

F13 0 0.526 0.822 1.045 1.142 1.198 1.224 1.236 1.242

F14 0 0.656 0.942 1.124 1.145 1.185 1.215 1.266 1.275

F15 0 0.554 0.852 0.999 1.256 1.456 1.654 1.789 1.952

F16 0 0.599 0.769 0.921 1.164 1.289 1.546 1.654 1.899

S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers… 1115

ADHESIVE STRENGTH

05

101520253035

F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 F13 F14 F15 F16

Batch No.

Adh

esiv

e st

reng

th

Fig. 1 Adhesive strength of formulation F1 – F16.

Swelling Index

00.10.20.30.40.50.60.70.80.9

11.11.21.31.41.51.61.71.81.9

2

0 1 2 3 4 5 6 7 8Time (hrs)

Swel

ling

Inde

x

F1F2F3F4F5F6F7F8F9F10F11F12F13F14F15F16

Fig. 2 Swelling index of formulation F1 – F16.

In vitro mucoadhesive Strength

Mucoadhesive strength of the tablet was measured on the modified physical balance. The design used for measuring the bioadhesive strength was shown in (Figure 3). The apparatus consist of a modified double beam physical balance in which the right pan has been replaced by a glass

slide with copper wire and additional weight, to make the right side weight equal with left side pan. A taflone block of 3.8 cm diameter and 2 cm height was fabricated with an upward portion of 2 cm height and 1.5 cm diameter on one side. This was kept in beaker filled with buffer media 0.1N HCl pH 1.2, which was then placed below right side of the

1116 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 3 • October-December 2010

B

G

E

A

I

H C D F

balance (Mahesh D. Chavanpatil et. al., 2006, Bhupinder Singh et. al., 2002, Kashappa Goud H. et. al., 2004, Owens TS, et. al., 2005, Bhupinder Singh et. al., 2006)

Fig. 3 In vitro Mucoadhesive Strength Measurement Apparatus (A) Right pan, (B) Left pan, (C) Teflon block, (D) Stomach membrane, (E) Teflon-coated

glass slide (F) Beaker containing 1.2 pH buffer, (G) Threads, (H) Pointer and (I) Scale

The procine gastric mucus membrane was used as model membrane and a pH 1.2 solution was used as the moistening fluid. The procine stomach mucosa (Ranga Rao et. al., 1989, Achar L et. al., 1994) was kept in Tyrode solution at 37◦C for 2 hours. The underlying mucus membrane was separated and washed thoroughly with a pH 1.2 solution. It was then tied to Teflon-coated glass slide and this slide was fixed over the protrusion in Teflon block using a thread. The block was then kept in beaker containing pH 1.2 buffer solution at the level that just touches the membrane. By keeping a 5g weight on the right pan, the two sides of the balance were made equal. The beaker with the Teflon block was kept below the left

hand set up of the balances. The tablet was struck on to the lower side of the left hand side pan. The 5 g weight from the right pan was then removed. This lowered the left pan along with the tablet over the membrane with a weight of 5 g. this was kept undisturbed for 3 minutes. Then, the weight on the right hand side was slowly added in an increment of 0.5 g till the tablet just separated from the membrane surface. The excess weight on right pan i.e., total weight minus 5 g was taken as a measure of the mucoadhesive strength. From the mucoadhesive strength, the force of adhesion was calculated using the following formula:

Force of adhesion (N) = Bioadhesive strength 9.81100

×

Bond strength (N/m2) = 2Force adhesion (N)

Surface area of tablet (m )

Results are summarized in (Table 3).

In-Vitro Dissolution Study

The in vitro drug release studies of the matrix tablets were conducted in USP type II dissolution apparatus equilibrated (TDT–08L, USP ETC-11LFC–12 Electro lab) at temperature 37±0.5oC and 50 rpm speed. The dissolution studies were carried out in triplicate for 12 hours in 900ml of gastric fluid (pH 1.2). The dissolution samples were collected at every 1 hour’s interval and replaced with an equal volume of gastric fluid to maintain the volume constant. The sample solution was diluted sufficiently and analyzed at 271 nm as mentioned in IP by a UV spectrophotometer (shimadzu, Kyoto, Japan). The amount of drug present in the sample was calculated with the help of appropriate calibration curves constructed from reference standard of the respective drug. Drug dissolved at specified period was plotted as a percent release versus time (hours) curve, depicted in (Figure 4).

Table 3 Swelling Index of Tablets of Batch F1 to F16.

Time (hrs) Batch no. 0 1 2 3 4 5 6 7 8

F1 0 0.624 0.852 1.041 1.166 1.248 1.250 -- -- F2 0 0.558 0.862 1.045 1.186 1.065 1.024 -- -- F3 0 0.672 0.918 1.122 1.245 1.327 1.347 1.306 -- F4 0 0.616 0.950 1.116 1.241 1.324 1.344 1.386 -- F5 0 0.120 0.399 0.605 0.852 0.934 1.140 1.181 1.201 F6 0 0.126 0.224 0.477 0.646 0.857 0.983 1.025 1.152 F7 0 0.204 0.532 0.660 0.830 0.915 1.000 1.043 1.085 F8 0 0.259 0.570 0.674 0.736 0.860 0.901 0.942 0.983

Table 3 Contd…

S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers… 1117

Time (hrs) Batch no. 0 1 2 3 4 5 6 7 8

F10 0 0.688 0.934 1.016 1.119 1.140 1.222 1.305 1.322 F11 0 0.599 0.803 0.926 1.008 1.131 1.172 1.254 1.295 F12 0 0.674 0.922 1.150 1.138 1.145 1.276 1.321 1.333 F13 0 0.526 0.822 1.045 1.142 1.198 1.224 1.236 1.242 F14 0 0.656 0.942 1.124 1.145 1.185 1.215 1.266 1.275 F15 0 0.554 0.852 0.999 1.256 1.456 1.654 1.789 1.952 F16 0 0.599 0.769 0.921 1.164 1.289 1.546 1.654 1.899

Cum % drug release v/s Time (hr)

0102030405060708090

100

0 1 2 3 4 5 6 7 8 9 10 11 12Time (hrs)

cum

. % d

rug

rele

ase

F1F2F3F4F5F6F7F8F9F10F11F12F13F14F15F16

Fig. 4 Percentage cumulative drug release of formulation F1 – F16.

Analytical method validation The method was validated according to the international conference of Harmonization guideline for validation of analytical procedure (ICH 2005). The validated parameters were accuracy and precision. The accuracy and precision were investigated at three concentration levels of tramadol HCl with six independent replicates on the same day and on the six consecutive days. The intraday and interday bias values were found to be less than 1.65% and 1.12% and intraday and interday relative standard deviation values were less than 2.16% and 1.84%, respectively.

Data Analysis The release data obtained from various batches was studied with respect to effect of drug: polymer ratio and diluents ratio. To analyze the mechanism of drug release from the formulation, the dissolution profile of all the batches was fitted to zero order, first-order, Higuchi, Hixon-Crowell, Korsemeyer and Peppas, and Weibull models to ascertain

the kinetic modeling of drug release (Sanford Bolton, 1997)

Results are summarized in (Table 5).

Stability Studies

The success of an effective formulation can be evaluated only through stability studies. The purpose of stability testing is to obtain a stable product which assures its safety and efficacy up to the end of shelf life at defined storage conditions and peak profile. Stability studies of optimized formulation (F15 and F16) of Tramadol HCl were placed on plastic tubes containing desiccant and stored at conditions, such as at room temperature, oven temperature (40±2oC and 75 ± 5%) and refrigerator (2-8oC) for a period of 6 month. The tablets were evaluated for mucoadhesive properties and in vitro drug release after 2, 4 and 6 months (Kulkarni G T et. al., 2004, Elizabeth B Vadas et. al., 2000, ICH 2005).

1118 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 3 • October-December 2010 Results obtained were compared with data obtained for zero time at room temperature, oven (40±2oC and humidity 75 ± 5%) and refrigerator condition.

The result of the mucoadhesive strength of optimized formulation (F15 and F16) after stability study shown in (Table 6).

Table 5 Kinetic values obtained from in vitro released data of different Tramadol HCl Mucoadhesive tablets formulations

Zero order plot First Order plot Higuch Model

Peppas Model Hixson- crowell

Formulation

K Correlation coefficient

K Correlation coefficient

Correlation coefficient

Slope (n)

Correlation coefficient

Correlation coefficient

F1 -13.600 0.9820 0.6911 0.8608 0.9928 0.5377 0.9934 0.9434

F2 -11.413 0.9784 0.5142 0.9415 0.9980 0.5178 0.9986 0.9881

F3 -9.6875 0.9621 0.4396 0.9547 0.9260 0.4958 0.9949 0.9062

F4 -10.800 0.9735 0.3661 0.9268 0.9540 0.7006 0.9438 0.9631

F5 -9.5172 0.9891 0.1805 0.5091 0.9912 0.7111 0.9954 0.9780

F6 -8.3734 0.9903 0.3228 0.8009 0.9906 0.6830 0.9946 0.9290

F7 -9.6523 0.9906 0.3447 0.9118 0.9879 0.7200 0.9931 0.9733

F8 -8.8515 0.9931 0.3120 0.8947 0.9821 0.7325 0.9924 0.9609

F9 -8.5790 0.9895 0.3244 0.8802 0.9767 0.7994 0.9939 0.9540

F10 -10.443 0.9855 0.1356 0.1968 0.9961 0.5778 0.9982 0.9879

F11 -8.7675 0.9611 0.2897 0.9888 0.9939 0.5626 0.9938 0.9979

F12 -8.3800 0.9819 0.3111 0.9489 0.9849 0.5526 0.9913 0.9879

F13 -6.8411 0.9821 0.1842 0.9575 0.9972 0.7815 0.9942 0.9884

F14 -6.8554 0.9413 0.2565 0.9154 0.9841 0.6266 0.9670 0.9699

F15 -7.1766 0.9989 0.1084 0.5241 0.9702 0.7836 0.9891 0.9460

F16 -7.3398 0.9966 0.2385 0.7941 0.9641 0.7639 0.9885 0.9040

Table 6 Stability studies of formulation as per ICH after 6 month.

F15 F16

Stability studies of formulation stored at 2-80C

Mucoadhesive strength (g)

Mucoadhesion force (N)

Mucoadhesive strength (g)

Mucoadhesion force (N)

29.58±0.042 0.2901±0.0004 31.69±0.071 0.3108±0.0006

Stability studies of formulation stored at Room temperature

29.48±0.042 0.2892±0.0004 31.465±0.035 0.3087±0.0003

Stability studies of formulation stored at 40±2oC and 75 ± 5%

29.33±0.016 0.2877±0.0001 31.54±0.035 0.3095±0.0003

S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers… 1119 Results and Discussion

Mucoadhesive drug delivery of tramadol HCl were formulated, by using various synthetic and natural polymers. Tramadol HCl mucoadhesive matrix tablet were prepared by wet granulation techniques. Tramadol HCl meets all the ideal characteristics to formulate in the form of oral drug delivery system.

The FTIR spectral analysis showed that there was no appearance or disappearance of any characteristic peaks of pure drug Tramadol HCl in the optimized formulation of drug and polymer (Figure 5, 6 and 7), which confirms the absence of chemical interaction between drug and polymers.

Fig. 5 IR spectra of pure drug Tramadol Hydrochloride.

Fig. 6 IR spectra of optimized formulation- F15.

1120 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue 3 • October-December 2010

Fig. 7 IR spectra of Optimized formulation- F16.

All the batches were evaluated for the physical properties and hardness of the tablet in the range of 6.4 to 7.5 (kg/cm2). Percentage weight loss in the friability test was less than 1% in all batches and all the batches contained Tramadol HCl within 100 ± 5% of labeled content. Overall, the prepared tablet batches were of good quality with regards to hardness, friability and drug content.

The in vitro mucoadhesive strength study was performed on the modified physical balance to measure the force (N) required for detaching the tablet. The bioadhesion characteristics were affected by the concentration of the mucoadhesive polymer. Viscosity of the polymer also affects the mucoadhesive strength of the tablet.

From the overall dissolution profile, it was concluded that the drug release rate decreased as concentration of the polymer increased, which was also affected by the type of polymer used. This can probably attributed to different diffusion and swelling behavior of the polymer.

The stability study showed that there was no change in the appearance and on drug release pattern of the tablet.

From the result of the dissolution data, the korsmeyer and peppas model found to be best fitted in all dissolution profile having a higher correlation coefficient. Thus, it was concluded that the drug release occurred via a diffusion mechanism and due to affinity of hydrophilic polymers towards water.

Conclusion The cram was undertaken with an endeavor to formulate and evaluate effect of hydrophilic polymer on release rate of mucoadhesive tablet. mucoadhesive tablet were formulated using, various hydrophilic polymers and their combinations in varying concentrations. Tablet were subjected to various evaluation parameters such as hardness, friability, drug content, mucoadhesive strength study and In vitro drug release study. It was revealed that all batches had acceptable physical parameters. The optimized formulation (F15 and F16) have good mucoadhesion along with in vitro drug release. It was observed that all batches followed the equation of zero order, higuchi matrix and peppas drug release profiles. Stability studies revealed that there was no significant change in the hardness, friability, drug content and in vitro dissolution profile of formulation F15 and F16. Thus these formulations were stable at different condition of temperature. The present study shows that there is influence of polymer on release profile of oral mucoadhesive tablet. The combination of hydrophilic synthetic (HPMC) and natural gum (Xanthan gum) can be used for designing oral mucoadhesive drug delivery system.

Acknowledgement The author’s are grateful to the Principal and Management of Shree H.N. Shukla Institute of Pharmaceutical

S.K. Singh, et.al. : Formulation and Evaluation of Mucoadhesive Tablet: Influence of Some Hydrophilic Polymers… 1121 Education and Research, Rajkot, Gujarat and Shree Leuva Patel Trust Pharmacy Mahila College, Amreli, Gujarat, for extending laboratory facilities and other required amenities to carry out this work.

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mucoadhesive interaction of poly (methacrylic acid) copolymer with rate mucosa. J.control Release. ; 1994; 31, 271-276.

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