Characterization of new crystalline forms of hydroxyprogesterone caproate

Publication date: 15 July 2017 Source:International Journal of Pharmaceutics, Volume 527, Issues 1–2 Author(s): Jeffrey Caplette, Timothy Frigo, Michael Jozwiakowski, Helene Shea, Mahmoud Mirmehrabi, Peter Müller A systematic polymorph screening process was conducted on the steroid hydroxyprogesterone caproate, which had only one previously described orthorhombic crystalline form (A), in order to fully elucidate its solid state properties. Cooling, anti-solvent and evaporative techniques largely reproduced the same polymorph, but slurries in various solvents over two days produced a new triclinic form (B). Experiments at different temperatures in ethyl acetate or isopropyl alcohol confirmed this was an enantiotropic system with a transition temperature of approximately 30°C. DSC was used to confirm the transition of Form B to Form A below the melting point. Form B was the thermodynamically stable form at room temperature, and 8% less soluble in a non-aqueous solvent mixture. In viscous solvents used commercially to dissolve the oil-soluble steroid for injection, solutions near the solubility limit can remain supersaturated after exposure to cooler temperatures for months. In resolving the crystalline structure of Form A, a third conformational polymorph was detected that exists only at −133 to −143°C; this monoclinic form was designated Form C, and converts back to Form A upon warming to room temperature. These studies have increased the understanding of this...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research