Efficient Screening of Pharmaceutical Cocrystals by Microspacing In-Air Sublimation

作者：Huimin Li, Lei Wang, Xin Ye, Changlin Yao, Shuhong Song, Yaqian Qu, Jinke Jiang, Hongshuai Wang, Peizhuo Han, Yang Liu, Xutang Tao · 发表于：Journal of the American Chemical Society · 年份：2024 · DOI：10.1021/jacs.4c00191 · 被引用次数：17 · 研究领域：Crystallography and molecular interactions、Crystallization and Solubility Studies、Enzyme Structure and Function

Cocrystal screening and single-crystal growth remain the primary obstacles in the development of pharmaceutical cocrystals. Here, we present a new approach for cocrystal screening, microspacing in-air sublimation (MAS), to obtain new cocrystals and grow high-quality single crystals of cocrystals within tens of minutes. The method possesses the advantages of strong designable ability of devices, user-friendly control, and compatibility with materials, especially for the thermolabile molecules. A novel drug-drug cocrystal of favipiravir (FPV) with salicylamide (SAA) was first discovered by this method, which shows improved physiochemical properties. Furthermore, this method proved effective in cultivating single crystals of FPV-isonicotinamide (FPV-INIA), FPV-urea, FPV-nicotinamide (FPV-NIA), and FPV-tromethamine (FPV-Tro) cocrystals, and the structures of these cocrystals were determined for the first time. By adjusting the growth temperature and growth distance precisely, we also achieved single crystals of 10 different paracetamol (PCA) cocrystals and piracetam (PIR) cocrystals, which underscores the versatility and efficiency of this method in pharmaceutical cocrystal screening.