Stanozolol-aromatic carboxylic acid crystalline complexes: flexible tautomeric/ionization states and supramolecular synthons

Stanozolol (STAN) is an androgenic and anabolic steroid medication used for the treatment of anemia, osteoporosis, and hereditary angioedema. This weakly basic compound possesses two energy-equivalent tautomers. These tautomeric forms and neutral/cationic states of STAN allow the presence of diverse inter-molecular interactions in its crystalline complexes. Two salts and five cocrystals of STAN have been reported with acidic guest molecules. Here, five novel crystalline complexes of STAN with benzoic acid derivatives, 2,6-dihydroxybenzoic acid (DBA), 2,5-dihydroxybenzoic acid (DHA), 1,2-benzenedicarboxylic acid (PHA), and gallic acid (GA), were successfully prepared. The molecular states of STAN and supramolecular synthons in these solid forms were disclosed via the solved single crystal structures and the C-13 solid state NMR spectra. Additionally, all the new anhydrous crystalline phases demonstrated favourable thermal stability and physical stability against hydration.