Development and Optimization of Repaglinide Amorphous Solid Dispersion Using Polymer Blends and Factorial Design for Enhanced Solubility and Dissolution

Abstract

The present study focuses on the fabrication and evaluation of an amorphous solid dispersion (ASD) system of repaglinide, a BCS Class II antidiabetic drug with poor aqueous solubility. The aim was to enhance the dissolution behavior and potential bioavailability of repaglinide using a polymer-based ASD approach. A polymer blend consisting of hydroxypropyl methylcellulose (HPMC), Pluronic F127, and polyethylene glycol (PEG 400) was used to prepare solid dispersions by reactive ball milling employing 1.7 mm zirconium beads. A 323^232 full factorial design was applied for formulation optimization. The prepared formulations were characterized using FTIR, XRD, and DSC to evaluate drug–excipient compatibility, amorphous nature, and stability. FTIR studies indicated good compatibility, while XRD and DSC confirmed the conversion of crystalline repaglinide into a stable amorphous form. In vitro dissolution studies showed significant enhancement in drug release. The optimized batch achieved more than 95% drug release and exhibited acceptable short-term stability.