Formulation and Evaluation of Sustained Release Matrix Tablets of Metformin Hydrochloride Using pH Dependent and pH Independent Methacrylate Polymers

Metformin hydrochloride is recommended globally as first line therapy due to its favorable profile on morbidity and mortality associated with type-2 diabetes mellitus. However, limitations of multiple dosing and risk of triggering gastrointestinal symptoms make its dose optimization difficult. Extended-release metformin matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L-100 and S-100) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio was evaluated. Among the different examined polymer blends, matrix tablets based on S-100/RLPO and S-100/RSPO mixtures gave the more sustained release pattern. The excipients used in this study did not alter physicochemical properties of the drug, as tested by Fourier transform Infrared Spectroscopy and the thermal analysis using differential scanning calorimetry. All the batches were evaluated for thickness, weight variation, hardness, and drug content uniformity. The in vitro drug dissolution study was carried out using USP 22 apparatus II, paddle method and the release mechanisms were explored. Mean dissolution time is used to characterize drug release rate from a dosage form and indicates the drug release retarding efficiency of polymer. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled to anomalous type. Fitting the data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. Research Article British Journal of Pharmaceutical Research, 1(2): 29-45, 2011 30