Pharmaceutical salt hydrates of vortioxetine with maleic acid and fumaric acid: Crystal structures, characterisation and solubility performance

Vortioxetine (VOT) is a serotonin (5-HT) receptor antagonist used for the treatment of major depressive disorder, but its poor solubility limits its absorption in vivo. This study aimed to improve the solubility properties of VOT and modify its physicochemical properties by combining it with pharmaceutically acceptable coformer molecules. In this work, two pharmaceutical salt hydrates of VOT with maleic acid (MA) and fumaric acid (FA) were successfully prepared by solvent evaporation and the liquid-assisted grinding method. The obtained salt hydrates were systematically investigated by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis techniques. The solubility of the salt hydrates was evaluated in water and pH 6.86 phosphate buffer medium. The results suggested that the two VOT salt hydrates exhibited increased solubility compared to VOT. The intrinsic dissolution rates (IDRs) of each salt hydrates was also determined, indicting that MA and FA were dissolution accelerators in water. (c) 2021 Elsevier B.V. All rights reserved.