Development and Evaluation of a Prolonged-Release Imeglimin Hydrochloride Matrix Tablet using Hydrophilic-Hydrophobic Polymer Blends

Abstract

Objective: The present work was aimed at designing and optimizing a prolonged-release matrix tablet of Imeglimin hydrochloride (500 mg) employing binary polymer combinations of hydroxypropyl methylcellulose (HPMC) K100M and Carbopol 940P as rate-controlling polymers for sustained antihyperglycemic action over 12 hours, with a target total tablet weight of 650 mg.Methods: Nine formulations (F1-F9) were developed via wet granulation using varying proportions of HPMC K100M and Carbopol 940P. Preformulation studies including Fourier-transform infrared (FTIR) spectroscopy were conducted to evaluate drug-excipient compatibility. 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 Imeglimin hydrochloride and the selected excipients. Among all developed batches, formulation F5, containing 6.2% w/w HPMC K100M and 1.5% w/w Carbopol 940P, exhibited the most desirable dissolution profile, releasing 76.5 ± 0.9% of the drug over a 12-hour period. The release followed near-zero-order kinetics (R² = 0.982) with an anomalous (non-Fickian) transport mechanism (release exponent, n = 0.56; R² = 0.990). 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 80.Conclusion: The optimized prolonged-release matrix tablet successfully sustained Imeglimin hydrochloride release over 12 hours and displayed excellent physicochemical stability, presenting a viable platform for twice-daily oral administration in the management of type 2 diabetes mellitus.