Formulation Development of Mucoadhesive Matrix Tablet for Metformin Hydrochloride: In-Vitro and In-Vivo Evaluation

 

Sheetal Dhar and Varsha Pokharkar*

Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, 411038, Pune, India.

*Corresponding Author E-mail: vbpokharkar@yahoo.co.in

 

ABSTRACT:

Of the various attempts to prolong the gastric residence time, use of mucoadhesive polymers is the most sought after. The main objective was to prolong the residence of metformin hydrochloride formulation in upper gastrointestinal tract. Herein we report a method for the preparation of mucoadhesive drug delivery system for metformin hydrochloride, a water soluble drug, using HPMC K4M, Carbopol 934P and Carbopol 971P as mucoadhesive and release controlling polymers. The selection of mucoadhesive polymer was done on the basis of water uptake, shear stress measurement and detachment force. The formulations were prepared by tablet compression method and were evaluated for water uptake, mucoadhesion, differential scanning calorimetry, in vitro and in vivo release. The water sorption studies of the formulation indicated a curvilinear relation for the drug: polymer ratio. The in vitro release studies revealed that the optimum combination of HPMC K4M and Carbopol 971P in the formulation leads to sustained release with a lower burst. The non invasive technique of gamma scintigraphy was explored which confirmed the exact position of the formulation within the gastrointestinal tract. Hence, it is concluded that the mucoadhesive formulation of metformin hydrochloride using mucoadhesive and release controlling polymers could sustain the drug release and remain in upper gastrointestinal tract so that the drug would be available in the dissolved form at the main site of its absorption.

 

KEYWORDS: Metformin hydrochloride, Mucoadhesion polymers, Dissolution kinetics, Gamma scintigraphy.

 


INTRODUCTION:

Metformin hydrochloride (Metformin HCl) is a biguanide glucose-lowering agent that has been successfully used for the management of type II diabetes mellitus (non-insulin dependent)1 alone or in combination with other hypoglycemic agents. This drug is prescribed as an adjunct to diet in mono-therapy of patients whose hyperglycemia cannot be satisfactorily managed on diet alone.2 It acts by decreasing hepatic glucose production and hepatic glucose output by reducing glycogenolysis and gluconeogenesis.3 It is a freely water-soluble drug with poor lipid solubility. The oral absorption of the drug is confined to upper part of the intestine i.e., the duodenum, jejunum and to a lesser extent in the ileum.  Due to this the absolute bioavailability of metformin HCl (500 mg metformin dose) after oral administration is only 50 %, with majority being absorbed within 6 h after ingestion 4 and the bioavailability decreases as the dose increases. After oral administration, about 50 % of the drug is excreted in urine and the remainder in faeces. Metformin HCl therapy is associated with gastrointestinal side effects that include gastric discomfort, nausea and diarrhea.

 

Stepensky et al.,5 have established a pharmacokinetic-pharmacodynamic rationale for development of metformin HCl controlled release formulation and concluded that clinical advantage could be obtained from gastro retentive systems that are retained in the stomach and produce a constant input of the drug to the effective site of absorption. The absorption of any drug from gastrointestinal tract (GI tract) is a complex procedure that includes many variables. Novel formulation strategies can be pursued for metformin, which may lead to an improvement in bioavailability, a reduction in dosing frequency, and/or a decrease in gastrointestinal side effects. Of the various attempts to prolong the gastric residence time, gastroretentive systems are the most sought after as they remain in the gastric region for several hours and therefore prolong the gastric residence time of drugs. In the literature many approaches have been studied to increase the gastric residence time of metformin HCl via sedimentation6, floatation7, modified shape systems8,9 or by the simultaneous administration of pharmacological agents10,11 that delay gastric emptying. Mucoadhesive drug delivery offers a number of applications for drugs with poor bioavailability because of narrow absorption window in the GI tract. Mucoadhesive drug delivery system retains the dosage form at the site of absorption and thus enhances the bioavailability. Adikwu et al.,12 studied mucoadhesive formulation of metformin HCl containing detarium gum as a mucoadhesive agent. The result indicated that detarium gum was a good excipient for the formulation of metformin mucoadhesive delivery systems, showed promising antidiabetic effect but should be cautiously used as it may lead to depressed blood glucose levels beyond the desired levels.

 

Thus the present studies were undertaken with an objective to conduct a comparative evaluation of various mucoadhesive polymers forming the basis to develop a controlled release mucoadhesive formulation of metformin HCl, which would retain the drug for a prolonged period of time in the upper part of GI tract so that the drug would be available in the dissolved form at the main site of its absorption i.e., proximal small intestine. The in-vitro mucoadhesive properties and the water uptake for various formulations were also determined. The drug release profiles and release kinetics were examined by fitting the drug release data into the basic Peppas model and in-vivo position of dosage form in the GI tract was evaluated by non-invasive technique gamma-scintigraphy. Thus mucoadhesive formulation of metformin HCl will help in improving the bioavailability of the drug and will stands an advantage over conventional dosage form, which needs to be administered twice or thrice a day.

 

MATERIALS AND METHODS:

Materials:

Metformin HCl was obtained as a gift sample from Micro Labs (Bangalore, India). Hydroxy propyl methyl celluloses (HPMC K4M, HPMC K15M and HPMC K100M) were gifted by Colorcon (Mumbai, India). Carbopol 934P and Carbopol 971P were obtained as gift from Noveon® (Mumbai, India). Chitosan was gifted by Central Institute of Fisheries (Cochine, India). Sodium alginate and Tragacanth were purchased from Loba Chemie Pvt. Ltd. (Mumbai, India). All other chemicals were of AR grade and were used as received.

 

Evaluation of Polymers:

The mucoadhesive polymers were evaluated for their viscosity, water sorption and adhesive properties using shear stress and detachment force measurement.

 

Viscosity:

Aqueous polymeric solutions (0.5% w/v) were prepared and the viscosity was determined at 25 oC using a Brookfield programmable DVII viscometer. In case of Carbopols the polymeric solution was neutralized with 0.01 N NaOH prior to determination of viscosity.

 

Water sorption studies:

Polymeric disks were prepared by compressing 300 mg of individual polymer sample in a 13 mm die punch set using 10-station, single rotary, B-tooling tablet machine (Rimek, Mini Press-I, Karnavati Engineering Ltd., Gujarat, India). The disks were then soaked in 25 ml of distilled water for 24 h. The swollen disks were removed and blotted with a filter paper to remove excess surface water. The swollen disks were immediately weighed to obtain the wet weight of compact (Ww) and dried at 50 oC till constant weight i.e. dry weight (Wd). The percent water uptake was determined using following equation.

% water uptake =              (1)

The study was performed in triplicate.

 

Shear stress measurement:

Shear stress measurement was performed by method reported by Rao et al.13 Two smooth polished plexiglass blocks were selected and one block was fixed with an adhesive on a leveled surface. A 3% w/v aqueous polymeric solution for each polymer was prepared and 500 mg of polymer solution was kept on the center of the fixed block. The second glass block was placed on top of first block and pressed by applying a load of 100 g such that the polymeric solution spreads as a uniform film between the two blocks for a period of 15 min. Care was taken to avoid entrapment of air bubbles. The shear stress was represented as the weight required to pull the upper block or make it slide down the base block in a direction parallel to the plane of contact.

 

Detachment force measurement:

The in-vitro mucoadhesion was measured in terms of force required to detach a tablet of test material from the mucosal layer of the sheep intestine. A two pan weighing balance was used for this study. Freshly slaughtered sheep intestine was cut into strips of 5-6 cm and kept in Tyrode solution prior to use. The strips were tied to a base in such a way that the mucosal surface faces upward. The polymeric disc, prepared in a manner as mentioned above (shear stress measurement), was fixed to the lower side of one of the pan using cynoacrylate adhesive and lowered till it touches the mucosal surface of the sheep intestine. A contact time of 5 min was given after applying a load of 100 g. Weights were added to the other pan of the balance and the total weight required to detach the tablet from the mucosal layer was determined. The study was performed in triplicate for each polymer.

 

Formulation of mucoadhesive matrix tablets:

The composition of various batches of mucoadhesive matrix tablet formulations is shown in Table 2. Individual components were weighed, sifted through a 40 # mesh sieve and then mixed using geometric dilution method. Metformin HCl (500 mg), which represented the dose per tablet, was weighed for all the batches. The mucoadhesive matrix tablets were prepared by compressing the blend in a 13 mm die punch set using 10-station, single rotary, B-tooling tablet machine (Rimek, Mini Press-I, Karnavati Engineering Ltd., Gujarat, India).

 

Evaluation of mucoadhesive matrix tablets:

Water sorption and detachment force measurement:

The water sorption studies and in-vitro mucoadhesion using detachment force measurement for the various formulation batches were performed as reported above for individual polymers. Detachment force measurement of the matrix tablets was conducted specifically for batches with the drug to polymer ratio 1:1. Tablets were also evaluated for mechanical strength using diametrical hardness tester (PTB, Pharmatest, India).The hardness of the tablets was in the range of 13-15 Kp.

Figure 1: Effect of drug: polymer ratio on the % water sorption of mucoadhesive formulation containing (a) individual polymers (b) combination of polymers.

 

Figure 2: In-vitro drug release from various batches of mucoadhesive formulation containing (a) single polymer (b) combination of polymers.

 

In-vitro release studies:

The drug release studies were carried out (in triplicate) using the Type II USP 24  dissolution testing apparatus (Electrolab, Mumbai) in 900 ml of pH 7.2 phosphate buffer at 100 rpm. The temperature was maintained at 37 oC ± 0.5 oC. The samples were withdrawn at preset time interval and replaced with fresh dissolution medium. The collected samples were diluted and the absorbance was measured spectrophotometrically (JASCO v530 UV/VIS/NIR spectrophotometer, Japan), at a wavelength of 233 nm. The analysis of data was done using PCP Disso V2.08 software.14

 

Figure 3: Peppas equation parameter for mucoadhesive matrix tablets containing single polymer (a) ‘n’ value (b) ‘K’ values.

 

Figure 4: Peppas equation parameter for mucoadhesive matrix tablets containing combination of polymer (a) ‘n’ value (b) ‘K’ values.

 

 


Table. 1. Comparative evaluation of mucoadhesive polymers.

Polymers

Shear Stress (g)*

Detachment Force (g)*

% Water Sorption

Viscosity (cP)

HPMC K4M

123.2 ± 2.4

50.8 ± 1.2

134%

1761

HPMC K15M

73 .0 ± 1.7

31.7 ± 1.5

80%

3282

HPMC K100M

54.2 ± 2.2

23.9 ± 1.1

108%

34889

Carbopol 934P

195.3 ± 3.7

63.5 ± 0.9

148%

14685

Carbopol 971P

216.9 ± 2.6

76.8 ± 1.3

175%

44774

Sodium Alginate

34.8 ± 2.9

23.2 ± 0.8

97%

259

Tragacanth

58.4 ± 1.6

47.5 ± 0.6

126%

306

Chitosan

107.5 ± 4.2

25.7 ± 1.3

114%

1209

Average of 3 readings ± standard deviation

 

Table. 2. Formulation batches of Metformin HCl mucoadhesive tablets.

Batch

HPMC K4M

Carbopol  934P

Carbopol 971P

Drug : Polymer Ratio*

% Water sorption

Detachment force measurement (g)

DA1

+

--

--

1:0.25

187

--

DA2

+

--

--

1: 0.5

570

--

DA3

+

--

--

1:1

495

35.2 ± 3.2

DB1

--

+

--

1:0.25

450

--

DB2

--

+

--

1: 0.5

636

--

DB3

--

+

--

1:1

531

44.2 ± 4.3

DC1

--

--

+

1:0.25

681

--

DC2

--

--

+

1: 0.5

998

--

DC3

--

--

+

1:1

595

52.2 ± 3.9

DAB1

+

+

--

1:0.25:0.75

648

--

DAB2

+

+

--

1:0.5:0.5

647

69.7 ± 5.4

DAB3

+

+

--

1:0.75:0.25

424

--

DBC1

--

+

+

1:0.25:0.75

318

--

DBC2

--

+

+

1:0.5:0.5

285

56.4 ± 6.2

DBC3

--

+

+

1:0.75:0.25

255

--

DAC1

+

--

+

1:0.25:0.75

667

--

DAC2

+

--

+

1:0.5:0.5

723

90.1 ± 4.8

DAC3

+

--

+

1:0.75:0.25

545

--

* The amount of metformin HCl per tablet was kept constant (500 mg)

 


Differential scanning calorimetry (DSC):

Thermograms of drug, excipients and powdered tablets were obtained using Mettler -Toledo DSC 821e (Mettler –Toledo, Switzerland) equipped with intracooler. Indium/Zinc standards were used to calibrate DSC temperature and enthalpy scale. Weighed sample of drug, excipients and powdered tablets were hermetically sealed in aluminum pans and heated at a constant rate of 10 oC/min, over a temperature of 25- 250 oC. Inert atmosphere was maintained by purging nitrogen gas (flow rate, 50 ml/min).

 

In-vivo studies:

The in-vivo study protocol was approved by the Institutional Ethical Committee of Poona College of Pharmacy. A written consent was obtained from volunteers and the study was supervised by expert radiologist and physician. The study was performed by gamma-scintigraphy in healthy male volunteers (25-30 years age and 55-65 kg body weight). Metformin HCl was radiolabeled with technetium (99mTc). Technetium offers several advantages in terms of its short half-life of 6 h and as it also allow very less amount of electron emission. It can be administered in milli curie amounts of 99mTc, resulting in very low radiation dose to the patient. Moreover, 99mTc is readily available in sterile, pyrogen-free state. Radionuclide Tecnicium (0.1 milli curie) was mixed thoroughly with ingredients and then compressed as described under preparation of tablets. Each volunteers ingested the tablet orally along with water. The volunteers were board in posterior position and visualized using a gamma camera (GE Millennium MPR Gamma Camera, Israel).

 

RESULTS AND DISCUSSION:

The design of a mucoadhesive matrix formulation of metformin HCl was addressed with an aim to retain the formulation in the upper part of GI tract where maximum absorption of the drug takes place and to sustain the drug release upto 8 hours for a prolonged action. The choice of mucoadhesive polymer was done on the basis of its viscosity, water uptake properties and adhesion properties like shear stress and detachment force.

 

Evaluation of mucoadhesive polymers:

The objective of carrying out shear stress measurement was to generate a comparative statement regarding the performance of different polymers. This proved beneficial in selecting the polymers for the formulation of matrices. Polymer water uptake is a property related to the mucoadhesion of a system. In the mucoadhesion process, a close polymer-mucosa contact leads to a consolidation step wherein several physico-chemical interactions occur to extend the mucoadhesion. This water-activated process causes an increase in the polymer chain mobility and facilitates interpenetration of polymer molecules with the mucus layer.15 Table 1 shows the comparative evaluation of various mucoadhesive polymers. This prompted the use of HPMC K4M, Carbopol 934P and Carbopol 971P for further study as they exhibited better water sorption and adhesion properties as compared to other polymers evaluated. The order of water uptake can be represented as HPMC K4M< Carbopol 934P< Carbopol 971P. The higher water uptake of carbopols can be explained on the basis of a synergistic mechanism. The presence of carboxylic groups in the polymer chain causes H-bonding and an increased water influx into the polymer matrix. Also, ionization of these carboxylic groups causes inter and intramolecular repulsion leading to uncoiling of chain and structure relaxation, thus promoting further uptake.16,17 Using these polymers either individually or in combination, mucoadhesive matrix tablets was formulated (Table 2).

 

Evaluation of mucoadhesive formulation:

The formulation batches were also subjected to water uptake and adhesion testing using detachment force measurement, to study the effect of drug on these properties.

 

Water uptake studies:

The effect of drug to polymer ratio (drug:polymer ratio) ranging from 1:0.25 to 1:1 on water uptake behavior of mucoadhesive formulations is shown in Fig. 1. Maximum water uptake was observed in case of Carbopol 971P containing formulations (DC1, DC2 and DC3) followed by formulations containing Carbopol 934P (DB1, DB2 and DB3) and HPMC K4M (DA1, DA2 and DA3) respectively. The observation is in accordance with the results for individual polymer. However, it was noted that % water sorption was found to be higher in formulation as compared to polymer alone (Table 1&2). Incorporation of highly water-soluble drug metformin HCl into the matrix leads to greater water uptake owing to osmotic effect. Subsequent solubilization and elution of the drug leaves behind pores or channels thus promoting further uptake. Changing the drug:polymer ratio from 1:0.25 to 1:0.5 causes an increase in the water uptake because of an increase in the polymer content. However, further increase in the polymer concentration (drug:polymer ratio 1:1) causes the curve to descend [Fig. 1(a)]. This may be attributed to an increase in the polymer bond percolation and formation of lesser number of pores and channels after the release of drug.18 Also an increase in polymer concentration led to formation of a viscous layer surrounding the tablet acting as a barrier for further water uptake and hydration of the tablet. As the viscosity of Carbopol 971P was maximum among the three polymers, descend of the curve was maximum for matrices containing Carbopol 971P followed by matrices containing Carbopol 934P and HPMC K4M respectively. Fig. 1(b) illustrates the effect of polymer composition on the water uptake behavior, in matrices containing combination of polymers. It was observed that changing the relative amount of first and second polymer in the matrix affected the water uptake behavior. In all the three cases i.e. DAB series, DAC series and DBC series, second polymer was more swellable as compared to first polymer and an increase in the amount of first polymer at the expense of amount of second polymer caused reduction in the water uptake. Interesting results were noted as there was a significant difference in the water uptake when the polymer composition varied, despite the small variation.  The water uptake increased in the order DBC series < DAB series < DAC series. These results differ from the observation for water uptake behaviors of individual polymers (HPMC K4M < Carbopol 934P < Carbopol 971P). Thus, although both Carbopols have greater water uptake compared to HPMC K4M, the matrix with combination of Carbopols (DBC1, DBC2 and DBC3) gave lowest water uptake. Carbopol 934P is a polymer, which contributes to the micro-viscosity within the gel system where as Carbopol 971P contributes to the macro-viscosity.19 Thus the combination of the two Carbopol, an increase in both micro and macro viscosity led to an increased resistance to water influx and hence a reduction in water uptake as compared to HPMC K4M:Carbopol combinations.

 

Detachment force measurement studies:

Table 2 shows the mucoadhesive strength of formulations with drug: polymer ratio of 1: 1. A direct correlation between water uptake and detachment force was seen. Thus, formulations with a higher water uptake also presented higher detachment force (DA3< DB3< DC3). A rise in water uptake facilitates the interaction between the polymer and mucus, thereby increasing the detachment force required. Though HPMC K4M shows less mucoadhesion, a significant increase in the detachment force was observed when it was used in combination with carbopols. Carbopols interact with water to produce a highly viscous gel layer. This gel layer acts as a barrier for further ingress of water into the formulation. This prevents the hydration of deeper layers of the matrix. HPMC K4M forms relatively less viscous chans in the matrix leading to hydration of deeper layers, increased interaction with the mucus layer and an increase in the mucoadhesion. Matrices with combination of Carbopol 934P and Carbopol 971P having lowest water uptake gave corresponding lower mucoadhesion strength.

 

In- vitro drug release studies:

The in vitro dissolution analysis was performed to obtain the dissolution release kinetics.  Fig. 2(a) & 2(b) show the drug dissolution profile for various batches. The data obtained from various batches were subjected to model fitting using the basic Peppas equation 2.

                              (2)

where ‘K’ is the constant incorporating the structural and geometric characteristics of the dosage form and is indicative of the release rate; ‘n’ is the release exponent indicative of the drug release mechanism and ‘Mt/M¥’ is the fraction of drug release which is a function of time ‘t’.

 

The release data for all the batches showed a good fitting to the Peppas equation with coefficient of correlation > 0.99. Fig. 3 & Fig. 4 relate the ‘n’ and ‘K’ value of Peppas equation to the drug: polymer ratio for various batches. For most of the batches the ‘n’ value was > 0.5 indicative of a non-Fickian release. In case of DA, DB and DC series, when the polymer content was low (drug: polymer ratio of 1:0.25) a low ‘n’ value (< 0.5) and a high ‘K’ value (> 6) was observed (Fig. 3) and the matrix was not able to sustain the drug release owing to low polymer content. An increase in polymer concentration (lower drug: polymer ratio) causes an increase in the viscosity of the gel and formation of a gel layer with longer diffusional path length leading to decrease in the release rate.

 

A comparison with respect to effect of type of polymer demonstrated a decrease in the ‘K’ value in the order DA series> DB series> DC series. The extent of inhibition of the drug diffusion through the gel layer is dependent on the gel layer characteristics. Unlike HPMC, the hydrogels of Carbopol 934P are not only entangled chain of polymers, but discrete microgels made up of highly crosslinked polymer particles giving it a fuzz ball type of gel structure in which the drug is dispersed.18 The crosslinked network enables the entrapment of the drug in the hydrogel domains and a decreased release rate. Carbopol 971P on the other hand is a slightly crosslinked polymer, which gives a fishnet gel structure upon hydration.18 Because of fewer crosslinks to constrain the polymer, it opens up easily and consequently the interstitial spaces between the swollen gel particles are eliminated and there is no significant difference between the micro and macro viscosity. A homogenous gel structure is formed and there are very few channels through which the drug may diffuse. Carbopol 971P swells at a faster rate and to a greater extent than either of the two polymers. The resultant gelation and sealing of surface pores limits the initial release of drug. The uptake curves then level off and the uptake of water continues slowly by diffusion through the growing gel layer, controlling the release rate of the drug.

 

Figure 5: DSC thermograms (A) pure drug, (B) HPMC K4M, (C) Carbopol 971 P and (D) tablet powder.

 

Formulations containing combination of polymers i.e. DAB, DAC and DBC series, significant difference was not observed in the release exponent ‘n’ when the ratio of polymers were changed (Fig. 4). This may be attributed to the fact that the overall drug: polymer ratio was kept constant even though the relative amounts of the constituent polymers were changed. Changes in release kinetics with respect to ‘n’ and ‘K’ values however were observed when the composition of the polymers in the formulation was changed. In DAB series a combination of HPMC K4M and Carbopol 934P was used. When either HPMC K4M or Carbopol 934P were replaced with a polymer having high water uptake behavior i.e. Carbopol 971P (DBC series and DAC series respectively) an increase in ‘n’ values (DAB series< DBC series< DAC series) and a corresponding decrease in ‘K’ values (DAB series> DBC series> DAC series) were noted. Thus from the results of water uptake studies, detachment force measurement studies and in vitro dissolution stuffy, formulation (DAC2 drug: polymer ratio 1:1) was further evaluated for differential scanning calorimetry and gamma-scintigraphy study.

 

 

Differential scanning calorimetry studies:

The DSC thermogram of metformin HCl, HPMC K4M, Carbopol 971P and tablet powder are shown in Fig. 5. The DSC scan of metformin HCl showed a single endotherm at 229.62 ºC ascribed to drug melting (-285.49 J/gm). Absence of endothermic peak for Carbopol 971P and HPMC K4M indicated the amorphous nature of the excipients used in the study. However, the endothermic peak of metformin HCl was found to be suppressed for tablet powder with HPMC K4M and Carbopol 971P with (-81.26 J/gm) energy required for melting. This may be due to the dilution effect after mixing with amorphous polymers and is in accordance with the ratio of polymers used. These results indicate absence of any interaction between drug and excipients.

 

In vivo scintigraphic studies:

In the present study the gastric emptying and intestinal transit of mucoadhesion formulation was studied by gamma-scintigraphy. Gamma scintigraphy has been used extensively as a noninvasive technique for in vivo evaluation of oral dosage forms. It is a well known technique to locate dosage form in GI tract on oral administration and has been used to locating matrices, granules, capsules and tablets, 20,21 enteric coated dosage forms,22 variations in GI transit of various dosage forms,23 and also to understand the mechanism of food effect as it relates to GI transit.24 Gamma scintigraphy study not only provide an insight into the fate of the oral dosage form but also allow to look on the systemic exposure of drug molecule in a particular dosage form in the GI tract to be evaluated and drug release/absorption to be examined. Gamma scintigraphic studies for batch DAC2 (drug: polymer ratio 1:1) revealed the exact location of oral mucoadhesive tablet in healthy volunteers (Fig. 6). Images were taken with volunteers in supine position immediately after administration of formulation at time intervals (0 h, 45 min, 2 h, 4 h and 8 h). The oral mucoadhesive tablet was found in the stomach for about 4 h and after 6 h the tablet was still located in the upper part of the intestine. Thus can be concluded that the mucoadhesive dosage form of metformin HCl could sustain the drug release and remain in upper GI tract so that the drug would be available in the dissolved form at the main site of its absorption.

 

Figure 6: Gamma scintigraphic image showing the release of metformin hydrochloride from mucoadhesive matrix formulation at different time intervals (note: marker for position of stomach).

 

CONCLUSION:

In conclusion, an intelligent combination of hydrophilic polymers is an interesting way of formulating oral controlled release metformin HCl mucoadhesive matrix tablet. The in-vitro release studies revealed that combination of HPMC K4M and Carbopol 971P in formulation led to an optimum combination of mucoadhesion and sustained release. Gamma-scintigraphy studies revealed that the formulation can be retained for longer time in upper part of the intestine where maximum amount of drug is required. However, further clinical pharmacokinetic studies are needed to establish the potential of mucoadhesive formulation to achieve maximum bioavailability.

 

ACKNOWLEDGMENT:

The authors are thankful to Dr Shrikant Solav, Spect Lab, Pune, India for providing the facility of gamma-scintigraphy.

 

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Received on 08.11.2009                             Modified on 21.12.2009

Accepted on 30.01.2010                            © RJPT All right reserved

Research J. Pharm. and Tech. 3(2): April- June 2010; Page 483-489