Preparation of iguratimod solid dispersion via hot-melt extrusion and investigation of factors affecting dissolution profile / 中国药学杂志

ABSTRACT

OBJECTIVE: To identify a suitable polymer system for iguratimod (T-614), a poorly water-soluble compound with high melting point, and prepare a chemically stable single phase solid dispersion (SD) of T-614 by hot-melt extrusion (HME) technique to enhance its dissolution rate. METHODS: Melting method and adsorption based screening techniques were utilized to screen hydrophilic polymers suitable for immediate release formulations. T-614 SDs were prepared with polymer carriers such as PVP/VA 64, Soluplus, HPMC AS-LF and HPC-SL via HME below the drug melting point, and suitable temperature and plasticizer for HME were chosen. The dissolution behaviors of SD powder and SD tablets were compared with those of T-614 powder and commercial T-614 tablets, respectively. State of T-614 in HME SDs was characterized by X-ray powder diffraction. The homogenous SD tablets were analyzed further for physical stability in an influencing factors test. The bioavailability of SD tablets was assessed in rats. RESULTS: Results of the screening studies demonstrated that PVP/VA 64, Soluplus, HPMC AS-LF and HPC-SL provided higher degree of miscibility and dissolution enhancement. The HWE SD tablets showed significantly enhanced dissolution. The supersaturation state of HME SD powder in water was maintained for at least 120 min, suggesting that PVP/VA 64 had an inhibitory effect on recrystallization of T-614 from a supersaturated solution. Samples prepared via HME at 160°C were substantially amorphous, which were unchanged in the influencing factors test at high temperature and strong light, but recrystallization occurred at high humidity. PEG1500 appeared to be a promising plasticizer. Same bioavailability was achieved when compared with commercial T-614 tablets. CONCLUSION: The polymersas carriers for T-614 SD have significant impact on the dissolution behavior and state of T-614. Using PVP/VA 64 as the carrier, hot-melt extrusion is an effective technology for improving the in vitro dissolution of T-614.