Pfund Laura Y, Matzger Adam J
Department of Chemistry and the Macromolecular Science and Engineering Program, University of Michigan , Ann Arbor, Michigan 48109, United States.
ACS Comb Sci. 2014 Jul 14;16(7):309-13. doi: 10.1021/co500043q. Epub 2014 Jun 20.
Methods capable of exhaustively screening for crystal polymorphism remain an elusive goal in solid-state chemistry. Particularly promising among the new generation of approaches is polymer-induced heteronucleation (PIHn), a tool utilizing hundreds of unique polymers for granting kinetic access to polymorphs. Here PIHn is redeployed in a high density format in which 288 distinct polymers, each acting as a heteronucleant, are arrayed on one substrate. This format allows determining the outcome of thousands of crystallizations in an automated fashion with only a few milligrams of sample. This technology enables the study of a broader range of targets, including preclinical candidates, facilitating determination of polymorphism propensity much earlier in the drug development process. Here the efficacy of this approach is demonstrated using four pharmaceutically relevant compounds: acetaminophen, tolfenamic acid, ROY, and curcumin.
能够彻底筛选晶体多晶型的方法在固态化学领域仍然是一个难以实现的目标。在新一代方法中，特别有前景的是聚合物诱导异相成核（PIHn），这是一种利用数百种独特聚合物来实现多晶型动力学可及性的工具。在此，PIHn以高密度形式重新部署，其中288种不同的聚合物（每种聚合物作为一种异质成核剂）排列在一个基底上。这种形式允许仅用几毫克样品以自动化方式确定数千次结晶的结果。这项技术能够研究更广泛的目标，包括临床前候选药物，有助于在药物开发过程中更早地确定多晶型倾向。在此，使用四种与药物相关的化合物（对乙酰氨基酚、托芬那酸、ROY和姜黄素）证明了这种方法的有效性。
