How cocrystallization affects solid-state tautomerism : Stanozolol case study

Three original cocrystals of stanozolol with monoacidic and diacidic coformers are presented and fully characterized in this study. Powder X-ray diffraction (PXRD) permits cocrystal formation to be highlighted, with the help of liquid-assisted grinding (LAG) from the two starting coformers. Single-crystal X-ray diffraction (SCXRD) gives a detailed structural characterization, which allows comparison with existing structures coming from the Cambridge Structural Database (essentially stanozolol solvates) and determination of structural similarities between the new cocrystal structures and the existing ones. As stanozolol can exist under two tautomeric forms (on its pyrazole moiety), statistical and theoretical studies have been performed in order to better apprehend the potential appearance of one of its tautomers at the cost of the other in crystal structures, and the eventuality of "freezing" the molecule in one of these forms by cocrystallization.