Development And Evaluation of a Controlled-Release Combination Tablet of Glimepiride and Metformin for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that requires sustained glycemic control to prevent long-term complications. Combination therapy with metformin hydrochloride and glimepiride is widely used due to their complementary mechanisms of action; however, conventional immediate-release formulations often require multiple daily dosing, leading to poor patient compliance and fluctuating plasma drug levels. The present study aimed to develop and evaluate a controlled-release bilayer tablet containing metformin hydrochloride as a sustained-release layer and glimepiride as an immediate-release layer for effective management of T2DM. Bilayer tablets were prepared by direct compression. The sustained-release layer of metformin hydrochloride was formulated using hydroxypropyl methylcellulose (HPMC K100M) and Carbopol 940, while croscarmellose sodium was employed as a super-disintegrant in the immediate-release layer of glimepiride. The prepared formulations were evaluated for pre- and post-compression parameters, drug content uniformity, in-vitro dissolution, release kinetics, and stability under accelerated conditions in accordance with ICH guidelines. The optimized formulation exhibited satisfactory physicochemical characteristics, including acceptable hardness, low friability, uniform weight variation, and high drug content. In-vitro dissolution studies demonstrated rapid release of glimepiride within 30 minutes and sustained release of metformin hydrochloride for up to 12 hours. Release kinetic analysis indicated a good fit with the Korsmeyer–Peppas model, suggesting an anomalous diffusion mechanism. Stability studies showed no significant changes in physical properties, drug content, or dissolution profile. The developed bilayer tablet successfully achieved a dual-release profile and represents a promising approach for improving patient compliance and therapeutic efficacy in the management of T2DM.