Preparation and Evaluation of Mucoadhesive Microcapsules of Flurbiprofen for Oral Controlled Release.

K.M. Lokamatha Swamy¹, D. Manjula²*, S.M. Shanta Kumar¹, N. Rama Rao¹, Somshekar Shyale¹ and Suma R.¹

¹Department of Pharmaceutics, V.L. College of Pharmacy, Raichur-584103, Karnataka, India.

²Department of Pharmaceutics, Dayananda Sagar College of Pharmacy, Bangalore-560078, India.

ABSTRACT:

The objective of this study was to develop, characterize and evaluate mucoadhesive microcapsules of flurbiprofen with a coat consisting of sodium alginate in combination with other mucoadhesive polymers such as sodium carboxy methylcellulose (sodium CMC), methyl cellulose (MC), carbopol and hydroxy propyl methyl cellulose (HPMC) by an emulsification-ionic gelation process for prolonged gastrointestinal absorption. The microcapsules were prepared by an emulsification-ionic gelation process. The microcapsules were evaluated for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy, and other parameters like drug entrapment efficiency, in vitro mucoadhesion by everted intestinal sac technique and in vitro drug release characteristics. The USP Rotating Basket method was selected to perform the dissolution profiles carried out in 900 ml of phosphate buffer of pH 7.2. The resulting microcapsules were discrete, small, and fairly spherical and free flowing. Microencapsulation efficiency was 60.92% to 87.74% and relatively high with alginate-carbopol and low with alginate-MC combinations. On the contrary, alginate-carbopol shown lower strength of mucoadhesion and high percentage of mucoadhesion was observed with alginate-MC combination. Flurbiprofen release from these mucoadhesive microcapsules was slow, extended over longer periods of time and depended on the combination of mucoadhesive polymer. The highest percentage of drug release was observed with alginate-hydroxy propyl methyl cellulose. Drug release kinetics from these formulations corresponded best to Higuchi model. The release of the model drug from these mucoadhesive microcapsules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Case II transport. By providing intimate contact of dosage form with the absorbing surface, bioavailability of drug could enhanced which in turn improves pharmacological effect. As a result, oral controlled release dosage form to avoid serious gastrointestinal adverse effects commonly associated with the model drug was achieved by the principle of mucoadhesion.

KEYWORDS: Flurbiprofen; Hydroxy propyl methyl cellulose; Sodium carboxy methyl cellulose; Methyl cellulose; Microcapsules

INTRODUCTION:

In the last two decades mucoadhesive polymers have received considerable attention as platforms for controlled drug delivery due to their ability to prolong the residence time of dosage forms as well as to enhance drug bioavailability. Mucoadhesion keeps the delivery system adhering to the mucus membrane. Mucoadhesive drug delivery systems offer the potential for improving the bioavailability of a wide range of drug products including biopharmaceuticals.^1-3 Several studies⁴ reported mucoadhesive drug delivery systems in the form of tablets, films, patches and gels for oral, buccal, nasal, ocular and topical.

The term “mucoadhesion” refers to the attachment of synthetic or natural macromolecules to a mucus-coated mucosal membrane⁵. A mucoadhesive polymer is natural or a synthetic polymer capable of producing an adhesive interaction with the mucus lining on the gastro intestinal mucosal membrane. The drug delivery system coated with mucoadhesive polymer binds to the mucin molecules in the mucus lining and helps to retain on the surface epithelium for extended periods of time.

Mucoadhesion is believed to occur in three stages: wetting, interpenetration and mechanical interlocking between mucin and polymer. According to electronic theory, mucoadhesion occurs from the formation of an electronic double layer at the mucoadhesive interface by the transfer of electrons between the mucoadhesive polymer and the mucin glycoprotein network⁶. Mucoadhesive polymers have been utilized in many different dosage forms in efforts to achieve systemic delivery of drugs through different mucosa^7,8. Mucoadhesive drug delivery system promise several advantages such as localization at a given target site, prolonged residence time at the site of drug absorption and intensified contact with the mucosa increasing the drug concentration gradient⁹. Hence, these systems draw attention in the search for increased bioavailability, improved patient compliance and decreased incidence of adverse drug reactions. Accordingly, diverse classes of natural and synthetic polymers have been investigated for potential use as mucoadhesive so far^10-14. Numerous studies have been carried out in order to achieve a desirable release rate of several non-steroidal ant-inflammatory drugs to treat rheumatoid arthritis, and osteoarthritis¹⁵. This study describes the development and evaluation of mucoadhesive microcapsules containing flurbiprofen employing various mucoadhesive polymers designed for oral controlled release. Flurbiprofen, one of the most useful NSAIDs which require controlled release due to its short biological half-life of 5.5 ± 1.4 h¹⁶ and serious gastrointestinal side effects such as inflammation, peptic ulceration with bleeding and perforation of the small or large intestine, was used as core in microencapsulation. The model drug is widely used in the treatment of periodontal diseases, rheumatoid arthritis, degenerative joint diseases, ankylosing spondylitis and allied conditions.

There are two broad classes of mucoadhesive polymers: hydrophilic polymer and hydrogels. Mucoadhesive polymers selected in the present study are Sodium CMC, MC, HPMC those belongs to the class of hydrophilic polymers containing carboxylic group. Whereas carbopol is hydrogen carrying anionic group, which belongs to the class of hydrogel that swell by absorbing water interacting through adhesion with the mucus that covers epithelia. Sodium alginate is the sodium salt of alginic acid, is also a best mucoadhesive polymer is selected to use in combination with other mucoadhesive polymers for microencapsulation of the model drug.

Mucoadhesive polymers offer a unique carrier system for many pharmaceuticals and can be tailored to adhere to any mucosal tissue, including those found in eyes, oral cavity, respiratory, urinary and gastrointestinal tract. Mucoadhesive polymers can be used not only for controlled release but also for targeted delivery of the drugs to specific sites in body. Consequently, polymeric science is on the way to explore newer mucoadhesive polymers with the added attributes of being biodegradable, biocompatible and bioadhesive for specific cells or mucosa, still a challenge and success is far ahead with so many difficulties. Hence present investigation is focused with a view to develop effective mucoadhesive microcapsules using existing mucoadhesive polymers in combinations, by evaluating the efficacy of polymers in controlling the release of drug from the dosage forms. Till now there are no reports of microencapsulation of flurbiprofen using above mentioned polymers in combination with sodium alginate.

MATERIALS AND METHODS:

Flurbiprofen was a gift sample from Ajantha Pharmaceuticals Bombay, Sodium carboxymethylcellulose, (sodium CMC, with a viscosity of 1500 ± 400 cps of 1% aqueous solution at 20^oC), methyl cellulose (with a viscosity of 65 cps of 2% aqueous solution at 20^oC) and hydroxypropyl- methylcellulose (HPMC, with a viscosity of 50 cps of 1% aqueous solution at 20^oC) and carbopol 934 were purchased from S.D Fine Chemicals Ltd. Mumbai. Sodium alginate and calcium chloride was procured from NR Chemicals and S.D Fine Chemicals Ltd. Mumbai, respectively. All other reagents used were of analytical grade.

Experimental Animals:

Swiss albino rats of male sex weighing between 300 to 400 g were used in this study. Animals were procured from Sri Venkateshwara Enterprises, Bangalore and were acclimatized for 7 days under standard housing conditions like, room temperature of 24±1°C; relative humidity 45-55% with 12:12 hour light/dark cycle. The animals were habituated to laboratory conditions for 48 hour prior to the experimental protocol to minimize any nonspecific stress. The Institutional Animal Ethics Committee (IAEC) of V.L College of Pharmacy, Raichur (Karnataka), India, approved the experimental protocol and animal studies were performed as per the rules and regulations in accordance with the guidelines provided by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) with registration number 557/02/C/CPCSEA.

Preparation of Microcapsules:

Microcapsules containing Flurbiprofen were prepared employing sodium alginate in combination with other mucoadhesive polymers such as sodium CMC, methyl cellulose, carbopol and HPMC as coat materials. The ionic-gelation process^17,18 is employed to prepare microcapsules. Sodium alginate (1.0 g) and the mucoadhesive polymer (1.0 g) were dissolved in purified water (32 ml) to form a homogeneous polymer solution. Core material, flurbiprofen (2.0 g) was added to the polymer solution and mixed thoroughly to form a smooth viscous dispersion. The resulting dispersion was then added in a thin stream to about 300 ml of groundnut oil while stirring at 400 rpm. The stirring was continued for 5 min to emulsify the added dispersion as fine droplets. Calcium chloride (10%w/v) solution (40 ml) was then added slowly while stirring for ionic gelation (or curing) reaction. Stirring was continued for 15 min to complete the curing reaction and to produce spherical microcapsules. The mixture was then centrifuged and the product thus separated was washed repeatedly with isopropanol to remove adhered oil and dried at 45⁰ for 12 h. The microcapsules prepared along with their coat composition are listed in Table 1.

Estimation of drug loading and encapsulation efficiency:

Flurbiprofen content in the microcapsules was estimated by extracting the drug into 7.2 pH phosphate buffer. The samples were then filtered and analyzed using UV spectrophotometric method based on the measurement of absorbance at 247 nm. The method was validated for linearity, accuracy and precision. The percentage of drug loading was then calculated as,

Amount of drug in the microcapsules

% Drug loading = ———————————— X 100

Mass of microcapsules

The microencapsulation efficiency was calculated using the formula,

Microencapsulation efficiency

Estimated percent drug content

= ————————————— X 100

Theoretical percent drug content

Surface Morphology:

Shape and surface characteristics of microcapsules was evaluated by using Scanning Electron Microscope (SEM). The purpose of SEM study is to obtain a morphological characterization of microcapsules. SEM photographs were taken with JEOL, JSM 5610-LV Scanning microscope (Japan) with a 20 kV accelerating voltage at 200x magnification (Fig-2, A) and at 100x magnification (Fig-2, B) at room temperature.

In Vitro Dissolution Study:

Microcapsules equivalent to 100 mg of flurbiprofen were filled in hard gelatin capsules (0 sizes) and evaluated for in vitro dissolution study for a period of 12 hours. It was carried out in accordance with the USP XX 1111 Dissolution Rate Test Apparatus, (Electro Lab- TDT 6P, Rotating basket apparatus) using 900 ml of phosphate buffer (pH 7.2, 37±0.5^o) at 75 rpm. A muslin cloth (200#) was tied over the basket to prevent the spillage of microcapsules. Samples (5 ml) were withdrawn at regular time intervals, filtered through a 0.45 µm membrane filter, diluted suitably and analyzed spectrophotometrically (Hitachi UV-2000, double-beam spectrophotometer, Japan) at 247 nm. An equal amount of fresh dissolution medium (37±0.5^o) was replaced immediately after withdrawal of the test sample. The amount of drug present in the samples was calculated with the help of appropriate calibration curve constructed from reference standards. The drug release experiments were performed in triplicate for each batch (n=3) in order to minimize the variational error. The percentage drug dissolved at different time intervals was calculated. The average values were used for further data treatment and plotting. Drug dissolved at specified time periods was plotted as percent release versus time (hours) curve.

Everted Sac Technique for Mucoadhesive Test:

The mucoadhesive property of the microcapsules was evaluated by an in vitro everted sac technique¹⁹. Everted sac experiments were performed using viable segments of rat jejunum. Unfasted rats (300-400 g, male) were sacrificed and intestinal tissue was excised and flushed with 10 ml of ice-cold phosphate buffered saline of pH 7.2 containing 200 mg / dl glucose (PBSG). Six centimetre segments of jejunum were everted using a stainless steel rod and lightly washed with PBSG to remove the contents. Ligatures were placed at both ends of the segment and the sac was filled with 1-1.5 ml of PBSG. Tissue was maintained at 4⁰C prior to incubation. The sacs were introduced into a 15-ml tube containing 60 mg of mucoadhesive microcapsules and 5 ml PBSG. The sacs were incubated at 37⁰ and agitated end-over-end. After 30 min, the sacs were removed and the solution of PBSG and unbound microcapsules was centrifuged for 30 min and the supernatant liquid was discarded. The microcapsules were washed and dried by lyophilization for 24-48 h. The percentage of bound capsules to the sac is calculated from difference in the weight of the residual microcapsules from the original weight of the microcapsules and reported as percent binding. The mucoadhesive test experiments were performed in triplicates (n=3) for each batch. This test is extremely simple and easily reproducible in any laboratory setting. The procedure has been shown in the cartoon in Fig.1

Figure 1. The everted sac technique procedure

Analysis of Release Kinetics:

In order to understand the mechanism and kinetics of drug release from the microcapsules, the in-vitro release data were fitted with the following mathematical models,

Zero-order kinetic equation²⁰…………Q_t= K₀ t …….. (1)

First-order kinetic²⁰…….ln Q_t = ln Q₀ – K₁ t …….. (2) and,

Higuchi release model²¹ _……….Q_t= K_h t^1/2 _…….. (3)

The following plots were made, Q_t Vs.t (zero-order kinetic model), log % drug retained Vs.t (first-order kinetic model), Q_t Vs t^1/2 (Higuchi model), where Q_t is the percent of drug released at time t, Q_{0 is} the initial amount of drug present in the microcapsules. K_0, K₁ and K_h are the zero order, first order and Higuchi dissolution rate constant of the equations respectively. But these models fail to explain

the drug release that was due to swelling (upon hydration) along with gradual erosion of the matrix. Therefore, the dissolution data were also fitted to the well-known exponential equation, the Korsemeyer and Peppas, which is often used to describe the drug release behavior from polymeric systems^22,23.

M_t/M_∞=K_ptⁿ…….. (4)

Where M_t/M_∞ is the fraction of drug released at time‘t’ and K_p is the rate constant and ‘n’ is the diffusional exponent, indicative of the drug release mechanisms. The value of ‘n’ is calculated for each batch from the slope of the plot of log of fraction of drug released (M_t/M_∞) vs. log time (t) according to Equation 4. Correlation coefficient ‘r’ values were calculated for the linear curves obtained by regression analysis of the above plots. In the case of

Table 1: Coat composition, physical characteristics and in-vitro mucoadhesion data of microcapsules prepared.

Formulation codes	Core-coat composition		Microencapsulation efficiency (%)	Particle size(µm)	Percent in vitro mucoadhesion
	Drug (g)	Polymer(1g) 1:1 ratio
F1	1	Alginate-Sod CMC	84.82 (1.72)*	37.34 ± 2.68	67.88 ± 1.92
F2	1	Alginate-MC	60.92 (1.83)*	82.73 ± 6.98	70.84 ± 1.87
F3	1	Alginate-HPMC	81.90 (1.36)*	65.94 ± 3.68	63.69 ± 2.30
F4	1	Alginate-Carbopol	87.74 (1.66)*	51 ± 6.62	59.54 ± 2.48

*Figures in parenthesis are coefficient of variance (CV) values.

Fickian release (diffusion-controlled release); ‘n’ value has a limiting value of 0.45 and 0.43 for release from cylinders and spheres, respectively. In Case II transport or relaxation-controlled delivery, the exponent ‘n’ is 0.89 and 0.85 for release from cylinders and spheres, respectively. The non-Fickian release or anomalous transport of drug occurred when the n values fell between the limiting values of Fickian and Case II transport for both shapes (i.e. >0.45 but <0.89). Occasionally, values of n > 0.89 or n > 0.85 for release from cylinders and spheres have been observed and considered to be Super Case II kinetics²⁴. These different mechanisms of drug release could result owing to relative rates of penetrant diffusion and macromolecular chain relaxation which determines the nature of the transport process and lead to a variety of penetrant transport phenomena such as Fickian, Case II, Super Case II and anomalous (non-Fickian).

Results:

Mucoadhesive microcapsules of flurbiprofen with a coat consisting of sodium alginate in combination with various mucoadhesive polymers (1:1) namely, sodium CMC, MC, HPMC and carbopol were prepared by an emulsification-ionic gelation process. Results obtained after evaluating different batches of flurbiprofen microcapsules for particle size, % microencapsulation efficiency and in vitro mucoadhesion values are averages of triplicates (n=3) and expressed as the mean ± standard deviation. The microencapsulation efficiency was in the range of 60.92% to 87.74% as shown in Table 1. The microencapsulation efficiency was relatively high with alginate- carbopol combination and low with alginate-MC combinations.

Particle size:

The particle size analysis of the microcapsules was done by using calibrated eye piece micrometer. Average and standard deviation of 100-200 particles was estimated. The average diameters of the resulting microcapsules were between 37.34 μm ± 2.68 to 82.73 μm ± 6.98 in size. Micromeritic analysis revealed that microcapsules prepared in this study are distributed in a relatively narrow range of diameter.

SEM Analysis:

Scanning electron micrograph (SEM) was used to evaluate the shape and surface characteristics of microcapsules. SEM photographs indicated microcapsules were fairly spherical, rough in surface, uniform in size and completely covered with the coat material as shown in Fig.2 (A and B).

Mucoadhesive Test:

The results of the everted sac experiments are presented as percent binding in Fig. 3. Everted intestinal sac test indicated fairly good mucoadhesive property of microcapsules and percent adhesion was high with alginate-methyl cellulose microcapsules and low with sodium alginate-carbopol microcapsules as shown in Table-1.

Figure 2: SEM Photographs of Microcapsules (A) In group (B) Single

Fig 3: Everted Sac Resusts

Table 2: Comparative Kinetic Values Obtained From Plots of Mucoadhesive Formulations.

Formulation codes	Kinetic models
	Zero-order		First-order		Higuchi model		Korsemeyer-Peppas model
	r	K0 (% mg/h)	r	K1Х10^2 ( h^-1)	r	Kh (%mg/h^1/2)	r	n
F1	0.9866	5.2324	0.9677	12.09	0.9679	22.4638	0.9750	0.9082
F2	0.9853	4.0415	0.9988	13.37	0.9878	24.7158	0.9785	0.8618
F3	0.9724	6.4451	0.9751	26.86	0.9912	29.7820	0.9839	0.7661
F4	0.9503	6.1963	0.9968	18.68	0.9958	27.4788	0.9878	0.6336

Release Kinetics:

Flurbiprofen release from the microcapsules was studied in phosphate buffer pH 7.2 for a period of 12 h. Drug release from the microcapsules prepared was slow and spread over extended periods of time as shown in Fig.4. The order of increasing release rate observed with various microcapsules was alginate-sodium CMC (F1) < alginate- MC (F2) < alginate-carbopol (F4) < alginate-HPMC (F3). The in vitro drug release profiles for all batches are shown in Table-2 and release data were applied on various kinetic models in order to find out the mechanism of drug release. The best fit with the highest correlation coefficient was shown in Higuchi, first-order and followed by zero-order equations. The rate constants were calculated from the slope of the respective plots. High correlation was observed in the Higuchi plot rather than first-order and zero-order models as shown in Fig.5. The drug release was proportional to square root of time which indicates that the drug release from mucoadhesive microcapsules was diffusion controlled. The percentage of drug released at 12 h from F1 and F2 formulations was nearly 80%, while the drug release from F3 and F4 formulations was more than 95% and 85% respectively as shown in Figure 4.

Fig 4: % Cumulative Drug Release from Flurbiprofen Microcapsules

DISCUSSION:

Low coefficient of variation (< 2.0%) in percent drug content indicated uniformity of drug content in each batch of microcapsules. The drug contents in microcapsules agreed well with the theoretical values and percent of drug entrapment was in the range of 60.92% to 87.74%. The microencapsulation efficiency was relatively high with alginate- carbopol combination. The microcapsules were found to be small, discrete, and fairly spherical and free flowing. Particle size analysis results showed that

microcapsules prepared in this study were distributed in a relatively narrow range of diameter from 37.34 μm to 82.73 μm. Microencapsulation efficiency was increased as the particle size decreased.

Fig 5: Higuchi plot of % Cumulative Drug Released Vs Square Root of Tim

SEM photographs revealed that microcapsules are fairly spherical containing rough surface and completely covered with the coat polymer. The smooth texture of microcapsule surface leads to weak mucoadhesive properties, while the coarser surface texture of microcapsules improves the mucoadhesion through the stronger mechanical interactions²⁵. As the presently investigated formulations consists of rough surface, they could facilitate intimate contact with absorption surface for longer period through the stronger mechanical interactions and hence enhance the bioavailability of drugs and thus contribute to the improved and better therapeutic performance of drugs.

In vitro mucoadhesion of microcapsules was the most important aspect of the present investigation. The everted intestinal sac technique is a passive test used for evaluation of bioadhesive interaction between polymer microcapsules in contact with everted intestinal tissue. Santos et al^[26] established a correlation between the CHAN technique and everted sac technique; both predict the strength of mucoadhesion in a very similar manner. So, one can confidentially utilize a single mucoadhesion assay to scan a variety of mucoadhesive polymers. A high percentage of binding indicates strong mucoadhesion of the polymer microcapsules to mucosal tissue. An effective mucoadhesive formulation not only should be able to adhere to the mucosal surface, but also should remain in the place for an extended period of time. Carbopol which belongs to the hydrogel class of mucoadhesive polymer, showed lower strength of mucoadhesion compared to other polymers used which are hydrophilic in nature¹⁹. Among other three hydrophilic polymers used, alginate-MC formulation exhibited highest strength of mucoadhesion. Overall the results of everted sac test indicate that microcapsules prepared with combinations of mucoadhesive polymers have potential to use as mucoadhesive drug delivery systems.

The Release of drug from microcapsules involves initial swelling followed by diffusion of the drug through dissolution media filled pores and channels. To know precisely whether Fickian or non-Fickian diffusion, the data obtained were also put in Korsemeyer-Peppas model in order to find out the value of ‘n’. The release kinetics for all the models is shown in table 2. In the present study, the value for ‘n’ determined from various formulations ranged from 0.633 to 0.908. In case of F1 and F2 the value of ‘n’ was found to be 0.908 and 0.861 respectively, with a correlation coefficient close to 0.98, indicating that the release mechanisms follow anomalous (non-Fickian) as well as Case II transport. The non-Fickian kinetics corresponds to coupled diffusion / polymer relaxation and Case II indicates the diffusion is much faster than the rate of the relaxation processes. Whereas F3 and F4 exhibited anomalous (non-Fickian) diffusion controlled release as the ‘n’ values fell between the limiting values of Fickian and Case II transport. The relaxation rate and diffusion rates are comparable²³. When the diffusion type is anomalous behavior, the relaxation and diffusion time are of the same order of magnitude. As the solvent diffuses into the hydrogel, rearrangement of chains does not occur immediately. The deviation of release kinetics from Fickian behavior has been associated with the finite rate at which the polymer structure rearranges, to accommodate water molecules, and has been observed for many hydrophilic polymer systems¹⁹.

Microcapsules of alginate-HPMC and alginate-carbopol gave relatively fast release when compared to alginate-sodium CMC and alginate-MC as shown in Fig-3. The resulting release profile of flurbiprofen from F1 and F2 formulations showed no significant difference in release rate. F1 formulation was found to cause highest retardation of drug. On the other hand, highest drug release was from F3 microcapsules while F2 and F4 gave an intermediate release profile between F1 and F3. Overall, the rate and extent of drug release was found highest with F3 formulation. The fact can be attributed to the hydrophilic nature of HPMC. When exposed to the dissolution medium, the solvent penetrates into the free spaces between macromolecular chains of HPMC. After salvation of the polymer chains, the dimensions of the polymer molecule increase due to the polymer relaxation by the stress of the penetrated solvent. This phenomenon is defined as swelling and it is characterized by the formation of a gel-like network surrounding the dosage form²⁷. This swelling and hydration property of HPMC causes an immediate formation of a surface barrier around the dosage form that eliminates burst release. The higher percentage (96%) of drug release at the end of 12 hour dissolution period can be attributed to the erosion of the matrix which takes place after complete hydration of outer layer. In this phase, the completely hydrated gel-layer start to disperse due to attrition process which furthermore allows the penetration of liquid to continue until the microcapsules disperse or disappears. Flurbiprofen release from alginate-sodium CMC (F1) and alginate-MC (F2) was slow, extended over a period of 12 h and these microcapsules were found to be suitable for oral controlled release formulations.

CONCLUSIONS:

Small sized spherical microcapsules with a coat consisting of alginate and mucoadhesive polymer like sodium CMC, MC, HPMC, carbopol could be prepared by emulsification-ionic gelation process. The microcapsules exhibited good mucoadhesive property in in-vitro everted sac test as the main objective was to provide an intimate contact of the dosage form with the absorbing surface and to increase the residence time to prolong the duration of action. Flurbiprofen release from these mucoadhesive microcapsules observed to be slow and extended over longer periods of time by using the principle of mucoadhesion. Drug release mechanism was non-Fickian as well as Case II transport and followed first order kinetics. Clearly each of the polymer combination used in the present investigation was capable of controlling the drug release rate from dosage form. Hence all the four formulations are useful for an oral controlled release of flurbiprofen. With the influx of a large number of new drug molecules from drug discovery, mucoadhesive drug delivery system which is emerging concept in drug delivery will play an important role in delivering these molecules.

ACKNOWLEDGEMENTS:

The authors are thankful to Academy of Medical Education, Raichur for its generous financial support to this research and Dr. Gururaj Neelgund, IISc, Bangalore for SEM analysis. Thanks are also extended to Dr. Somasekhar Shyale for useful discussions.

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Received on 13.04.2010

Accepted on 30.05.2010

© A&V Publication all right reserved

Research Journal of Pharmaceutical Dosage Forms and Technology. 2(3): May-June 2010, 241-246