FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE SUSTAINED-RELEASE AND EMPAGLIFLOZIN IMMEDIATE-RELEASE BILAYER TABLETS

Objective: The present study aimed to formulate and evaluate bilayer tablets containing sustained-release Metformin hydrochloride and immediate-release Empagliflozin for the management of Type 2 diabetes. Methods: The wet granulation technique was employed to formulate a sustained-release Metformin HCl layer and an immediate-release Empagliflozin layer. The impact of varying concentrations of independent variables (HPMCK100M and Carbopol 971P) on drug release at different times was evaluated using a 2-factor central composite design (CCD)with five central replicates.The formulation was optimized using responsesurface methodology (RSM) through CCD, and optimal levels of polymers were determined using surface plots and response optimizer. In-vitro release data observed from the optimized formulation were subjected to pre- and post-compression analysis and fitted into various drug release kinetic models. Results: Using response surface methodology (RSM), the optimized formulation contained 17.9% HPMCK100M and 3.8% Carbopol, respectively. Various parameters were noted: hardness, 21.33kg/cm²; friability, 0.23%; and uniformity of content for empagliflozin (98.23%), whichwas within the limit.The assay percentages of metformin and empagliflozin were 95.27% and 96%, respectively. In vitro drug release at 1, 6, 10, and 12 hours is 20.08%, 67.02%, 87.06%, and 97.52%, respectively, which is comparable to the predicted drug release by RSM.The optimized model accurately predicted the drug release profile, with a chi-square test (χ² = 0.436, df = 3) and a similarity factor (f2) of 82.54showing no significant differences.Similarly, the drug release of the optimized formulation followed the Korsmeyer–Peppas model (R²= 0.9986), indicating a combination of diffusion and polymer relaxation mechanisms inthe drug release process. Conclusion: In conclusion, we developed an optimized fixed-dose bilayer formulation of sustained-release metformin HCl and immediate-release empagliflozin using a central composite design. The optimized formulation exhibited predictable release kinetics, best described by the Korsmeyer-Peppas model, confirming anomalous transport driven by both diffusion and polymer relaxation. This work presents how experimental design and mechanistic modeling can be integrated to aid in the development of bilayer tablet formulations, thereby validating the growing body of knowledge in this field. Clinically, the formulation presents a promising approach for improving glycemic control, enhancing patient compliance, and reducing healthcare costs.