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

Li, Li-Yang; Du, Rong-Kai; Du, You-Li; Zhang, Chun-Jing; Guan, Su; Dong, Chang-Zhi; Zhang, Lei

doi:10.3390/cryst8020085

Open AccessArticle

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

by

Li-Yang Li

¹,

Rong-Kai Du

¹,

You-Li Du

¹,

Chun-Jing Zhang

¹,

Su Guan

¹,

Chang-Zhi Dong

^2,3 and

Lei Zhang

^1,3,*

¹

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China

²

Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Paris CEDEX 13, France

³

MOE Joint International Research Laboratory of Synthetic Biology and Medicine, South China University of Technology, Guangzhou 510006, China

^*

Author to whom correspondence should be addressed.

Crystals 2018, 8(2), 85; https://doi.org/10.3390/cryst8020085

Submission received: 5 January 2018 / Revised: 2 February 2018 / Accepted: 2 February 2018 / Published: 5 February 2018

(This article belongs to the Special Issue Novel Pharmaceutical Cocrystals and Their Applications)

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Abstract

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.

Keywords: febuxostat; minoxidil; salt solvates; crystal structure

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MDPI and ACS Style

Li, L.-Y.; Du, R.-K.; Du, Y.-L.; Zhang, C.-J.; Guan, S.; Dong, C.-Z.; Zhang, L. Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance. Crystals 2018, 8, 85. https://doi.org/10.3390/cryst8020085

AMA Style

Li L-Y, Du R-K, Du Y-L, Zhang C-J, Guan S, Dong C-Z, Zhang L. Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance. Crystals. 2018; 8(2):85. https://doi.org/10.3390/cryst8020085

Chicago/Turabian Style

Li, Li-Yang, Rong-Kai Du, You-Li Du, Chun-Jing Zhang, Su Guan, Chang-Zhi Dong, and Lei Zhang. 2018. "Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance" Crystals 8, no. 2: 85. https://doi.org/10.3390/cryst8020085

APA Style

Li, L.-Y., Du, R.-K., Du, Y.-L., Zhang, C.-J., Guan, S., Dong, C.-Z., & Zhang, L. (2018). Febuxostat-Minoxidil Salt Solvates: Crystal Structures, Characterization, Interconversion and Solubility Performance. Crystals, 8(2), 85. https://doi.org/10.3390/cryst8020085

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

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