Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance

Three febuxostat-minoxidil salt solvates with acetone (ACE), tetrahydrofuran (THF) and isopropanol (IPA) are synthesized by solvent-assisted grinding and characterized by infrared (IR), nuclear magnetic resonance (1H-NMR), single crystal and powder X-ray diffraction (PXRD), thermogravimetry (TG) and...

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Bibliographic Details
Main Authors: Li-Yang Li, Rong-Kai Du, You-Li Du, Chun-Jing Zhang, Su Guan, Chang-Zhi Dong, Lei Zhang
Format: Article
Language:English
Published: MDPI AG 2018-02-01
Series:Crystals
Subjects:
Online Access:http://www.mdpi.com/2073-4352/8/2/85
Description
Summary:Three febuxostat-minoxidil salt solvates with acetone (ACE), tetrahydrofuran (THF) and isopropanol (IPA) are synthesized by solvent-assisted grinding and characterized by infrared (IR), nuclear magnetic resonance (1H-NMR), single crystal and powder X-ray diffraction (PXRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). These febuxostat-minoxidil salt solvates feature isostructural with the same stoichiometries (1:1:1 molecule ratio). The proton transfers from the carboxylic group of febuxostat (FEB) to imino N atom of minoxidil (MIN), which forms the motif with combined R 2 2 (9) R 4 2 (8) R 2 2 (9) graph set in the three solvates. The solvents occupy the different positions related to the motif, which results in the apparent differences in PXRD patterns before/after desolvation although they are isostructures. The FEB-MIN·THF was more thermostable than FEB-MIN·ACE and FEB-MIN·IPA relative to solvent removal from DSC patterns, which is different from the results from the solvent-exchange experiments in chemical kinetics. All three salt solvates exhibit increased equilibrium solubility compared to FEB in aqueous medium.
ISSN:2073-4352