Novel Sustained-Release Nateglinide Microspheres: In Vitro Evaluation for Improved Antidiabetic Therapy

Abstract

Nateglinide, a short-acting oral hypoglycemic agent, requires multiple daily administrations due to its short half-life, adversely impacting patient compliance. The purpose of this study was to develop and optimize a sustained-release microsphere formulation of Nateglinide to prolong drug release and improve therapeutic adherence in the management of type 2 diabetes. Nateglinide-loaded microspheres were successfully formulated using the solvent evaporation method with PLGA as the polymer and PVA as the stabilizer. Five formulations (F1–F5) with varying drug-to-polymer ratios (1:1 to 1:5) were developed, among which F4 (1:4 ratio) was optimized. F4 exhibited optimal particle size, excellent flow properties, high encapsulation efficiency (96.3%), and drug content (19.26%). SEM revealed spherical microspheres with moderate porosity, while DSC and FTIR confirmed drug–polymer compatibility and amorphous dispersion. The zeta potential (−23.7 mV) indicated stable dispersion. In vitro studies showed sustained drug release (97% over 24 hours), following first order and Higuchi models. Stability studies confirmed minimal degradation under storage conditions. The optimized Nateglinide microspheres provided sustained release, stable physicochemical properties, and effective kinetics, indicating potential to reduce dosing frequency and improve compliance in type 2 diabetes management.