title: Structures and physicochemical properties of vortioxetine salts.
abstract: In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKabeing greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl), p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT-IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The acidic proton is transferred to the secondary N atom on the piperazine ring of VT, forming the charge-assisted hydrogen bond N+-H...X-(X = Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were carried out in distilled water (pH = 7.0) to compare the solubilities of the salts with that of VT. The VT-ASP-H2O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT-ASP-H2O (1:1:2) is a high solubility salt that is stable in a slurry experiment at 298 K in 95% ethanol. The experimental data for the VT-ASP-H2O (1:1:2) salt identify it as a promising drug candidate.
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China.
authors.forename: Xinbo
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Hu
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, People's Republic of China.
authors.forename: Suxiang
authors.initials: S
authors.lastname: Wu
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, People's Republic of China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Ye
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, People's Republic of China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Sun
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Gu
authors.affiliation: Zhejiang Jingxin Pharmaceutical Co., Ltd, Xinchang, Zhejiang 312500, People's Republic of China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Zhejiang Jingxin Pharmaceutical Co., Ltd, Xinchang, Zhejiang 312500, People's Republic of China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000928:Antidepressive Agents / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D018054:Hydrobromic Acid / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D015394:Molecular Structure; D010226:Parabens / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D012439:Saccharin / Q000737:chemistry; D012492:Salts / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013440:Sulfides / Q000737:chemistry*; D000078784:Vortioxetine; D014961:X-Ray Diffraction
chemical_list: D000928:Antidepressive Agents; D010226:Parabens; D010879:Piperazines; D011208:Powders; D012492:Salts; D013440:Sulfides; D001224:Aspartic Acid; D018054:Hydrobromic Acid; D000078784:Vortioxetine; D012439:Saccharin; C038193:4-hydroxybenzoic acid; D006851:Hydrochloric Acid
keywords: antidepressant; salt; solubility; vortioxetine