Cocrystal Screening of Stanolone and Mestanolone Using Slurry Crystallization

A slurry crystallization technique was used in cocrystal screening of two nonionizable pharmaceutical host compounds, stanolone and mestanolone, with 11 pharmaceutically acceptable guest acids. Crystallization was performed simply by adding crystallization solvents to solid mixtures of a host and a guest, which had been prepared using lyophilization of their dimethyl sulfoxide solution. Powder X-ray diffraction and thermogravimetric/differential thermal analysis were used to identify new solid forms. Two resultant new forms, stanolone l-tartaric acid 1:1 cocrystal and mestanolone salicylic acid 1:1 cocrystal, were characterized using single-crystal X-ray diffraction. The hosts, despite having the same steroidal skeleton and the same functional groups that form strong hydrogen bonds, each formed a cocrystal with a different guest molecule. All functional groups of the host and guest molecules that form strong hydrogen bonds were engaged in hydrogen bonding, but, despite the highly analogous molecular structures of the hosts, the two cocrystals exhibited dissimilar crystal structures. The present study shows the slurry technique to be viable and practical for cocrystal screening and demonstrates the importance not only of hydrogen bonding but also of geometric fit in cocrystal formation.