Pharmaceutical salt and salt hydrates of vortioxetine with sulfonic acid to ameliorate the solubility and hygroscopicity via the charge-assisted hydrogen bond assembly

Salt forms of vortioxetine (VOT) with three sulfonic acids have been designed and prepared in 1 : 1 stoichiometry ratio, and their crystal structures and physicochemical properties have also been characterized in detail. Three salt forms are assembled by the charge-assisted hydrogen bond recognition. In particular, the water molecules have featured distinct structural skeletons and resulted in different thermal behaviors in two salt hydrates by high temperature SXRD experiments. The salt forms can increase the VOT solubility in all cases, and sulfanilic acid salt features the best solubility performance with approximately 17-fold increment over the free VOT in water. The hygroscopicity of the sulfanilic acid salt is also advantageous compared with that of free vortioxetine and other salt hydrates. This successful attempt implies that the molecular recognition of charge-assisted hydrogen bonds is an effective strategy to improve the physicochemical properties of vortioxetine, and provides an effective route for designing and manufacturing novel solid states of vortioxetine.