Glimepiride is a third-generation sulfonylurea used in the management of type 2 diabetes mellitus. Despite its efficacy, glimepiride's therapeutic application is limited by its poor water solubility and short biological half-life, necessitating frequent dosing to maintain effective plasma concentrations. To overcome these challenges, the development of a sustained release formulation through solid dispersion techniques presents a promising strategy.

Objective: This study aims to formulate and evaluate a sustained release solid dispersion of glimepiride to enhance its solubility, bioavailability, and therapeutic efficacy, while reducing dosing frequency.

Solid dispersions of glimepiride were prepared using various hydrophilic carriers, including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose (HPMC), via solvent evaporation and melting techniques. Different ratios of drug to carrier were tested to identify the optimal formulation. The prepared solid dispersions were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X- Ray Diffraction (XRD) to assess drug-polymer interactions, thermal properties, and crystallinity changes.

The optimal solid dispersion was incorporated into sustained release matrix tablets using direct compression. Various excipients such as hydroxypropyl methylcellulose (HPMC K15M), ethyl cellulose, and carbopol were utilized to achieve sustained release profiles. Tablet formulations were evaluated for physical properties including hardness, friability, and uniformity of weight.

Dissolution tests were conducted using USP Type II dissolution apparatus in phosphate buffer (pH 7.4) to simulate intestinal conditions. The release profiles were analyzed using mathematical models (zero-order, first-order, Higuchi, and Korsmeyer-Peppas) to determine the kinetics and mechanism of drug release.

The FTIR and DSC analyses confirmed the absence of significant drug-polymer interactions, indicating chemical stability. XRD patterns revealed a reduction in the crystallinity of glimepiride in the solid dispersions, suggesting enhanced solubility. Among the carriers tested, HPMC-based solid dispersions exhibited the highest solubility enhancement. The sustained release tablets showed satisfactory physical properties, with hardness and friability within acceptable limits.

The in vitro dissolution studies demonstrated a controlled and sustained release of glimepiride over 24 hours. The release kinetics followed the Higuchi model, indicating diffusion-controlled release. The optimized formulation achieved a significant improvement in the dissolution rate compared to pure glimepiride, with approximately 80% drug release at 24 hours, demonstrating its potential for sustained therapeutic effect.