Isomorphous Crystals Formed by the Similar Supramolecular Motifs in Sorafenib Hydrochloride and Regorafenib Hydrochloride Salts

Sorafenib and regorafenib (or fluoro-sorafenib) are multikinase inhibitors active in the treatment of various human cancers, but their solubilities are very poor. To improve their solubilities, in this study, sorafenib hydrochloride (SorHCl, I) and regorafenib hydrochloride (RegHCl, II) have been prepared and their crystal structures were characterized. Their solubility properties in water were evaluated. Intriguingly, they are isomorphous crystal structures with the same space group and the similar unit cell dimensions, which were caused by the similar supramolecular patterns resulted by the formation of N-HCl- hydrogen bond instead of hydrogen bond between the protonated pyridinium cation and counterion. Moreover, the solubility properties displayed identical profiles. It may be concluded that a similar crystal structure leads to a comparable solubility profile.