Cocrystals of Favipiravir: Improved Physicochemical Properties and Solution Stability Study

作者：Huimin Li, Lei Wang, Guanying Xie, Changlin Yao, Shuhong Song, Yaqian Qu, Peizhuo Han, Hongshuai Wang, Yanyan Sun, Huachang Wu, Xutang Tao · 发表于：Crystal Growth & Design · 年份：2023 · DOI：10.1021/acs.cgd.3c00805 · 被引用次数：11 · 研究领域：Crystallography and molecular interactions、Crystallization and Solubility Studies、Energetic Materials and Combustion

Favipiravir (FPV) is used in the treatment of viral influenza, but it faces challenges due to its moderate solubility and poor tabletability. As an oral drug, it is necessary to develop a drug candidate that can improve its solubility and bioavailability. In addition, solution instability is one of the challenging issues of FPV cocrystals that should be noticed. On the premise of maintaining the solution stability, we aim to improve the solubility and tabletability through the preparation of FPV cocrystals to provide good alternative drugs. Herein, besides FPV-PHBA, we report the preparation and characterization of three new cocrystals of FPV with 3-hydroxybenzoic acid (FPV-3HBA, 1:1), 3,5-dihydroxybenzoic acid (FPV-3,5DHBA, 1:1), and also a cocrystal-hydrate with 3,4-dihydroxybenzoic acid (FPV-3,4DHBA-H 2 O, 1:1:1). All the cocrystals were characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Hirshfeld surface (HS) analysis, and molecular electrostatic potential surface (MEPS) analysis. Furthermore, we evaluated the solubility, tabletability, hygroscopicity, and accelerated stability of the cocrystals and explored the relationship between their structure and properties. The cocrystals exhibited a 6-fold increase in solubility and improved tabletability while maintaining good stability under certain temperature and humidity conditions...