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Structures and physicochemical properties of vortioxetine salts
Author(s) -
Zhou Xinbo,
Hu Xiurong,
Wu Suxiang,
Ye Jiali,
Sun Mengying,
Gu Jianming,
Zhu Jianrong,
Zhang Zhongliang
Publication year - 2016
Publication title -
acta crystallographica section b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.604
H-Index - 33
ISSN - 2052-5206
DOI - 10.1107/s2052520616010556
Subject(s) - solubility , chemistry , dissolution , differential scanning calorimetry , salt (chemistry) , hydrobromic acid , powder diffraction , hydrochloric acid , inorganic chemistry , nuclear chemistry , crystallography , organic chemistry , physics , thermodynamics
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 Δp K a being 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–H 2 O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT–ASP–H 2 O (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–H 2 O (1:1:2) salt identify it as a promising drug candidate.