State Key Laboratory of Crystal Materials, Institute of Crystal Materials, Shandong University, Jinan 250100, P. R. China.
School of Physics and Photoelectronic Engineering, Ludong University, Yantai 264025, P. R. China.
J Am Chem Soc. 2024 May 1;146(17):11592-11598. doi: 10.1021/jacs.4c00191. Epub 2024 Apr 17.
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.
共晶筛选和单晶生长仍然是药物共晶发展的主要障碍。在这里，我们提出了一种新的共晶筛选方法，即微间距空气升华（MAS），可在数十分钟内获得新的共晶，并生长高质量的共晶单晶。该方法具有设备设计能力强、用户友好的控制和与材料兼容性等优点，特别是对于热不稳定的分子。该方法首次发现了一种新型的药物-药物共晶法维帕他韦（FPV）与水杨酰胺（SAA），其物理化学性质得到了改善。此外，该方法还成功地培养了 FPV-异烟酰胺（FPV-INIA）、FPV-脲、FPV-烟酰胺（FPV-NIA）和 FPV-三甲胺（FPV-Tro）共晶的单晶，并且首次确定了这些共晶的结构。通过精确调整生长温度和生长距离，我们还获得了 10 种不同扑热息痛（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高效性。
