Development and Evaluation of Prolonged Release Metformin Hydrochloride Matrix Tablets Using Hydrophilic–Hydrophobic Polymer Blends
DOI:
https://doi.org/10.22270/ajprd.v14i4.1853Abstract
Objective: The present work was aimed at designing and optimizing a prolonged-release matrix tablet of metformin hydrochloride (500 mg) employing binary polymer combinations to achieve sustained antihyperglycemic action over 24 hours and improve patient compliance through once-daily dosing.
Methods: Nine formulations (F1–F9) were developed via wet granulation using varying proportions of hydroxypropyl methylcellulose (HPMC) K100M and Carbopol 940P as rate-controlling polymers. Preformulation studies including Fourier-transform infrared (FTIR) spectroscopy were conducted to evaluate drug–excipient compatibility. The micromeritic properties of granules and physicomechanical characteristics of compressed tablets were assessed. In vitro drug release was performed in pH 6.8 phosphate buffer using a USP Type II dissolution apparatus at 37 ± 0.5 °C and 50 rpm with sinkers. Dissolution kinetics were analyzed by zero-order, first-order, Higuchi, Korsmeyer–Peppas, and Hixson–Crowell models. Accelerated stability studies were conducted as per ICH Q1A(R2) guidelines.
Results: Compatibility studies confirmed the absence of physicochemical interactions between metformin hydrochloride and the selected excipients. Among all developed batches, formulation F5, containing 20% w/w HPMC K100M and 5% w/w Carbopol 940P, exhibited the most desirable dissolution profile, releasing 95.5 ± 0.9% of the drug over a 24-hour period. The release followed near-zero-order kinetics (R² = 0.985) with an anomalous (non-Fickian) transport mechanism (release exponent, n = 0.58; R² = 0.992). All formulations complied with pharmacopeial limits for weight variation, hardness, friability, and content uniformity. Accelerated stability testing (40 ± 2 °C / 75 ± 5% RH, 90 days) demonstrated no significant change in drug content or release behaviour; the similarity factor (f₂) remained above 82.
Conclusion: The optimized prolonged-release matrix tablet successfully sustained metformin hydrochloride release over 24 hours and displayed excellent physicochemical stability, presenting a viable platform for once-daily oral administration in the management of type 2 diabetes mellitus.
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