Development and Characterization of a Novel Sustained-Release Formulation of Glimepiride for Improved Glycemic Control

Abstract

Compliance among patients is impeded by glimepiride's brief half-life and frequent dosing necessities, notwithstanding its prevalent application as an oral antidiabetic agent. The objectives of this study were to enhance glycemic control and reduce dosage frequency through the development and characterisation of a novel sustained-release (SR) formulation of glimepiride. The sustained release formulation was generated using hydroxypropyl methylcellulose (HPMC K100M) as a rate-controlling polymer by the solvent evaporation process. In vitro drug release, drug entrapment efficiency, zeta potential, particle size, and polydispersity index (PDI) were evaluated. Wistar rats were employed for pharmacokinetic studies, while streptozotocin-induced diabetic rats were utilized to assess the hypoglycemia effect. The improved SR formulation exhibited an average particle size of 152.4 ± 4.8 nm, a PDI of 0.214 ± 0.02, and a zeta potential of -23.6 ± 1.5 mV. The release profile adhered to a zero-order kinetics (R² = 0.991), with an entrapment efficiency of 94.2 ± 1.1%, and a sustained in vitro release of 92.6 ± 1.4% after 24 hours. The pharmacokinetic analysis revealed that the AUC₀-∞ increased by 1.9-fold, and the t₁/₂ length extended from 5.4 ± 0.3 hours (with standard medication) to 14.2 ± 0.6 hours. After 24 hours, the SR formulation significantly reduced fasting blood glucose levels by 68.4% in vivo, compared to a 42.1% reduction with the traditional formulation (p < 0.01). In comparison to the conventional glimepiride formulation, the novel glimepiride SR formulation demonstrated superior glycemic control, enhanced bioavailability, controlled drug release, and improved entrapment efficiency. This formulation may improve therapeutic outcomes and patient adherence to diabetic treatment.