Abstract
GI197111X is a 5‐alpha reductase inhibitor for the treatment of androgenetic alopecia. Equilibrium solubilities of GI197111X were determined in multiple solvents or cosolvents. A polymorph screen was conducted using suspension equilibration and solution recrystallization methods. Single crystals were grown from pyridine/water and crystal structure was determined using a Bruker SMART diffractometer. Crystal structure data were imported into Cerius2 to provide visualization of the crystal structure and calculation of the simulated X‐ray powder diffraction (XRPD) pattern. The solubility of GI197111X was low at 25°C in all vehicles suitable for animal and human dosing. The solubility of 6.4 mg/mL in Capmul MCM made it the only choice for a soft gel dosage form for phase I/II. Solution recrystallization and suspension equilibration of GI197111X have produced only one crystal form. Crystal structure data: orthorhombic P21 21 21; a = 10.8960(6) Å, b = 11.5683(6) Å, c = 20.9019(11) Å; unit cell volume 2634.65(24) Å3; Z = 4; calculated density = 1.248 g/cc. The molecule has seven chiral centers, and single‐crystal analysis eliminated all possible stereoisomers except the expected conformation or its enantiomer. Hydrogen bonds occur from both carbonyl oxygens to an H–N group. Simulated vacuum‐based crystal morphology (habit) calculated using the Bravais–Friedel–Donnay–Harker, Growth Morphology, and Hartman‐Perdok modules in Cerius2 was a close match to the morphology observed by light microscopy.