Iohara Daisuke, Anraku Makoto, Uekama Kaneto, Hirayama Fumitoshi
Faculty of Pharmaceutical Sciences, Sojo University.
DDS Research Institute, Sojo University.
Chem Pharm Bull (Tokyo). 2019;67(9):915-920. doi: 10.1248/cpb.c18-00752.
Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives have gathered considerable attention to control crystallization behavior of drugs. This review focuses on the use of hydrophilic cyclodextrins (CDs) as additives for controlling drug crystallization. CDs affect the crystallization of drugs in solution and in solid state based on a host-guest interaction. For example, 2,6-di-O-methyl-β-CD and 2-hydroxybutyl-β-CD suppressed solution-mediated transition of drugs during crystallization by the host-guest interaction; as a result, metastable forms selectively precipitated in solution. The use of CDs in crystal engineering provided an opportunity for the detection of a new polymorph by changing the crystallization pathway. It was also possible to modify crystal morphology (i.e., crystal habit) by selective suppression of crystal growth on a certain direction based on the host-gust interaction. For solid formulation, stable amorphous drug/CDs complex under humid conditions was prepared using two different CDs. An overview of some recent progress in the use of CDs in crystal engineering and in amorphous formulation is described in this review.
控制药物结晶是制剂前研究中的重要问题之一。近年来，包括使用特制添加剂在内的先进方法已引起了人们对控制药物结晶行为的广泛关注。本综述聚焦于使用亲水性环糊精（CDs）作为添加剂来控制药物结晶。基于主客体相互作用，CDs会影响药物在溶液和固态中的结晶。例如，2,6-二-O-甲基-β-环糊精和2-羟丁基-β-环糊精通过主客体相互作用抑制了结晶过程中溶液介导的药物转变；结果，亚稳态形式在溶液中选择性沉淀。在晶体工程中使用CDs为通过改变结晶途径检测新的多晶型物提供了机会。基于主客体相互作用，通过选择性抑制特定方向上的晶体生长来改变晶体形态（即晶习）也是可能的。对于固体制剂，使用两种不同的CDs制备了在潮湿条件下稳定的无定形药物/CDs复合物。本文综述了CDs在晶体工程和无定形制剂应用方面的一些最新进展。
