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.

中文翻译：

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通过微间距空气升华有效筛选药物共晶

共晶筛选和单晶生长仍然是药物共晶开发的主要障碍。在这里，我们提出了一种共晶筛选的新方法，即微间距空气升华（MAS），以获得新的共晶并在数十分钟内生长出高质量的共晶单晶。该方法具有器件可设计性强、控制方便、与材料尤其是不耐热分子相容等优点。通过该方法首次发现了法匹拉韦（FPV）与水杨酰胺（SAA）的新型药物-药物共晶体，其显示出改善的理化性质。此外，该方法被证明可有效培养 FPV-异烟酰胺（FPV-INIA）、FPV-尿素、FPV-烟酰胺（FPV-NIA）和 FPV-氨丁三醇（FPV-Tro）共晶的单晶，以及这些共晶的结构被首次确定。通过精确调整生长温度和生长距离，我们还获得了10种不同的扑热息痛（PCA）共晶和吡拉西坦（PIR）共晶的单晶，这凸显了该方法在药物共晶筛选中的通用性和高效性。