Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2484215 | Journal of Pharmaceutical Sciences | 2016 | 6 Pages |
Abstract
Three 1:1 salts containing vortioxetine (VOT), an orally antidepressant drug, and 3 aryl monoacids have been designed and successfully prepared by liquid-assisted grinding based on the ÎpKa rule. The C-O bond lengths (â¼1.25 Ã
) in the COOH groups show that the proton transfer has occurred from aryl monoacid to piperazine N1 atom of vortioxetine in the crystal structures. Three salts feature cyclic [2 + 2] structural units through R44 (12) N-H···O hydrogen bonding interactions which result in the remarkable thermal stabilities, and VOT-p-aminobenzoic acid shows 2-dimensional framework by linking cyclic [2 + 2] units through additional hydrogen bonding interactions. The equilibrium solubility of VOT in VOT-p-aminobenzoic acid salt can be largely improved up to 0.50 mg/mL (about 450% above the free base) at 25°C in water, which also accelerates the intrinsic dissolution rate.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Sai-Fei He, Xian-Rui Zhang, Shuo Zhang, Su Guan, Jing Li, Shan Li, Lei Zhang,