Amorphous solid dispersion of diosmetin prepared by hot melt extrusion: Processability, stability and dissolution behavior

Abstract

Diosmetin (DM) is a natural flavonoid with poor water solubility and low bioavailability. This study aimed to improve the dissolution of DM by preparing amorphous solid dispersions (ASDs) using hot melt extrusion (HME) with chitosan lactate (CL) and polyvinylpyrrolidone K30 (PVP-K30). The processability of the formulations was evaluated during extrusion, while the extrudates were characterized for thermal behavior, crystallinity, intermolecular interaction, drug content, physical stability, and in vitro dissolution in simulated gastric fluid (pH 1.2) and phosphate buffer (pH 6.8). Thermal behaviors and PXRD diffractograms confirmed the transformation of crystalline DM into the amorphous form after HME, while Fourier Transform Infrared Spectroscopy (FT-IR) suggested intermolecular interactions between DM and the polymer matrix, contributing to stabilization of the amorphous form. The ASDs showed acceptable drug content and remained physically stable after storage for 30 days. The ASDs exhibited formulation dependent and pH-dependent dissolution profiles, with only certain formulations showing improved DM dissolution compared with crystalline DM. Rapid hydration and gel formation of CL could be observed and they promoted particle agglomeration and hindered drug diffusion from the polymer matrix. These findings indicate that the dissolution performance of CL/PVP-K30-based ASDs is governed by the balance between the amorphization and the dissolution retarding effects of polymer hydration, highlighting the importance of polymer selection for optimizing HME formulations of poorly water-soluble drugs.