Amorphous-based controlled-release gliclazide matrix system.

The aim of this study was to develop a hydrophilic oral controlled release system (CRS) using the amorphous form of gliclazide, a BCS class II compound, listed on the WHO list of essential medicines. For this purpose, spray-dried dispersions (SDDs) of gliclazide were produced using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) or copovidone as carrier under fully automated conditions. The solid-state properties of prepared SDDs were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), and Fourier transform infrared spectroscopy (FTIR). Supersaturated micro-dissolution testing of SDDs in fasted state-simulated intestinal fluid showed prolonged supersaturation state, with solubility increases of 1.5- to 4.0-fold. Solubility and stability characteristics of the most desirable SDDs in terms of relative dissolution area under the curves (AUCs) (AUC(SDD)/AUC(crystalline)) and stable supersaturated state concentration ratio up to 180 min (C180/Cmax) were determined. The optimized gliclazide-SDD amorphous forms were included into matrix tablets with HPMC blends using compaction simulator. Developed matrix systems were subjected to standard USP dissolution testing. Dissolution profiles obtained were linear with different slopes indicating varying rates of dissolution. Six-month storage stability testing was performed, and dissolution profiles remained stable with "similarity factor" (f 2 = 85). Results show that the use of various HPMCAS as a drug carrier in the spray-drying process produces homogeneous single-phase SDDs which are stable and promising for inclusion into HPMC-based hydrophilic matrix systems.