山东大学陶绪堂团队报道了微间距空气升华法高效筛选药物共晶。相关研究成果发表在2024年4月17日出版的《美国化学会杂志》。

共晶筛选和单晶生长仍然是药物共晶发展的主要障碍。

该文中，研究人员提出了一种新的共晶筛选方法，即空气中微空间升华（MAS），以获得新的共晶体，并在几十分钟内生长出高质量的共晶体单晶。该方法具有器件可设计性强、控制方便、与材料相容性强的优点，特别是对不耐热分子。该方法首次发现了一种新的法匹拉韦（FPV）与水杨酰胺（SAA）的药物-药物共晶，其理化性质得到了改善。

此外，该方法对培养FPV-异烟酰胺（FPV-INIA）、FPV-尿素、FPV--烟酰胺（FPV-NIA）和FPV-丁三醇（FPV-Tro）共晶的单晶是有效的，并首次测定了这些共晶的结构。通过精确调节生长温度和生长距离，研究人员还获得了10种不同的对乙酰氨基酚（PCA）共晶和吡拉西坦（PIR）共晶的单晶，这突出了该方法在药物共晶筛选中的多功能性和效率。

附：英文原文

Title: Efficient Screening of Pharmaceutical Cocrystals by Microspacing In-Air Sublimation

Author: Huimin Li, Lei Wang, Xin Ye, Changlin Yao, Shuhong Song, Yaqian Qu, Jinke Jiang, Hongshuai Wang, Peizhuo Han, Yang Liu, Xutang Tao

Issue&Volume: April 17, 2024

Abstract: 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.

DOI: 10.1021/jacs.4c00191

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c00191