Solubilization and Solid-State Characterization of a Poorly Soluble 5-Alpha Reductase Inhibitor

GI197111X, a 5-alpha reductase inhibitor intended for treating androgenetic alopecia, was found to have low solubility at 25°C in all tested solvents suitable for animal and human use, with a solubility of 6.4 mg/mL in Capmul MCM being the only viable option for a soft gel dosage form in phase I/II trials. The study involved determining equilibrium solubilities, conducting a polymorph screen, and analyzing the crystal structure using a Bruker SMART diffractometer. The crystal structure was orthorhombic with specific unit cell dimensions and a calculated density of 1.248 g/cc. The molecule featured seven chiral centers, and single-crystal analysis confirmed the expected conformation or its enantiomer. The study also simulated and observed the crystal morphology, which matched closely with the calculated model.