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Crystals 2018, 8(9), 352;

Improved Solubility of Vortioxetine Using C2-C4 Straight-Chain Dicarboxylic Acid Salt Hydrates

School of Chemical Engineering and Resource Recycling, Wuzhou University, Wuzhou 543000, China
Author to whom correspondence should be addressed.
Received: 5 August 2018 / Revised: 25 August 2018 / Accepted: 31 August 2018 / Published: 2 September 2018
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The purpose of this study was to improve the solubility of vortioxetine by crystal engineering principles. In this paper, three C2-C4 straight-chain dicarboxylic acid salt hydrates of vortioxetine (VOT-OA, VOT-MA-H2O, and VOT-SUA-H2O, VOT = vortioxetine, OA = Oxalic acid, MA = malonic acid, SUA = succinic acid) were synthesized and characterized by single X-ray diffraction, powder X-ray diffraction, and differential scanning calorimetry. The single crystal structure of three salts reveals that vortioxetine has torsional flexibility, which can encourage VOT to allow combination with aliphatic dicarboxylic acids through N+-H···O hydrogen bonds. The solubility of all salts exhibits a dramatic increase in distilled water, especially for VOT-MA-H2O salt, where it shows the highest solubility, by 96-fold higher compared with pure vortioxetine. View Full-Text
Keywords: vortioxetine; dicarboxylic acid; salt hydrates; crystal structure vortioxetine; dicarboxylic acid; salt hydrates; crystal structure

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Gao, L.; Zhang, X.-R.; Yang, S.-P.; Liu, J.-J.; Chen, C.-J. Improved Solubility of Vortioxetine Using C2-C4 Straight-Chain Dicarboxylic Acid Salt Hydrates. Crystals 2018, 8, 352.

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