Studies on Preformulation and Formulation of JIN-001 Liquisolid Tablet with Enhanced Solubility

Abstract

This study aimed to develop a heat shock protein 90 (Hsp90) inhibitor liquisolid tablet with improved solubility to overcome low bioavailability issues. As an active pharmaceutical ingredient (API), JIN-001, a novel Hsp90 inhibitor, was reported to have substantial in vitro antiproliferative and in vivo antitumor activity; however, JIN-001 was a crystalline solid with very low solubility in an aqueous solution, and therefore, Capryol 90, which has excellent solubilization ability, was selected as an optimal liquid vehicle based on solubility studies. JIN-001 liquisolid (JLS) powder was successfully prepared by dissolving JIN-001 in Capryol 90 and mixing colloidal silicon dioxide (CSD) used as an oil adsorption agent. The prepared JLS was confirmed to be amorphous. Based on the result of the solubility test of JLS, compared to JIN-001, the solubility of the former was significantly improved in all solvents regardless of pH. JLS tablets were prepared through wet granulation using JIN-001 and stable excipients based on the compatibility test. The developed JLS tablet significantly increased the drug release rate in all tested solutions; however, the liquisolid method had no significant effect on bioavailability in the pharmacokinetics study in beagle dogs. In conclusion, the liquisolid system influenced the solubility and dissolution rate of JIN-001.

Keywords

• JIN-001
• heat shock protein 90 inhibitor
• capryol 90
• colloidal silicon dioxide
• liquisolid
• solubility