Merck KGaA, Darmstadt, Germany.
Drug Discov Today. 2023 May;28(5):103527. doi: 10.1016/j.drudis.2023.103527. Epub 2023 Feb 14.
Whereas pharmaceutical co-crystals are widely described as tool to improve solubility and dissolution behavior of poorly soluble drugs, so far less focus has been on their potential role to facilitate pharmaceutical manufacturability. This review summarizes recent developments in co-crystal research regarding new trends in co-crystal preparation routes and control of solid-state material attributes. Also, recent literature was reviewed to assess risks for co-crystals in formulation processes. A growing number of publications suggest that co-crystals show potential to specifically improve mechanical properties such as tabletability and compressibility, which can often be linked to intrinsic features of crystal structure properties. However, such trends must be treated with care, as molecular structures in reported co-crystal studies are not representative in some structural parameters governing also solid-state behavior (smaller molecular weight, more balanced hydrogen bond donor versus acceptor counts) compared to recent market approved small molecule drugs.
虽然制药共晶被广泛描述为改善难溶性药物的溶解度和溶解行为的工具，但迄今为止，人们对它们在促进药物可制造性方面的潜在作用关注较少。本综述总结了共晶研究的最新进展，包括共晶制备途径的新趋势和对固态材料属性的控制。此外，还对最近的文献进行了综述，以评估共晶在制剂过程中的风险。越来越多的出版物表明，共晶有可能特别改善机械性能，如可压性和可压缩性，这通常与晶体结构特性的固有特征有关。然而，必须谨慎对待这些趋势，因为与最近市场批准的小分子药物相比，报告的共晶研究中的分子结构在一些控制固态行为的结构参数方面没有代表性（分子量更小，氢键供体与受体的比例更平衡）。
