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添加剂调控药物晶体形貌研究进展

Research progress on additives regulating drug crystal morphology

  • 摘要: 药物晶体形貌会影响产品下游加工与制剂溶解性能,实现晶体形貌调控在制药领域具有十分重要的意义。近年来,添加剂应用于药物晶体形貌调控受到广泛关注,特定的添加剂可以通过影响晶体生长调节晶体形貌,但目前添加剂调控晶体形貌的作用机制仍不完全清楚,使用添加剂调控晶体形貌仍处于试错阶段。本综述阐述了聚合物(主要为药物辅料)与小分子(包括表面活性剂与结构类似物)两类添加剂对药物晶体形貌的调控作用机制,包括干扰晶体-溶液界面处溶质的附着、改变晶体表面能、干扰溶质溶剂相互作用等,实现晶体生长过程调控,进而改变晶体形貌。本综述总结了这两类添加剂在溶液结晶中改善药物晶体形貌方面的应用,以期为溶液结晶中使用添加剂调控药物晶体形貌提供理论指导。

     

    Abstract: Crystal morphology significantly affects downstream processing and the solubility of pharmaceutical products. Therefore, controlling crystal morphology is of great importance in the pharmaceutical industry. In recent years, the use of additives to regulate drug crystal morphology has received widespread attention. Specific additives can influence crystal morphology by modulating crystal growth. Still, the underlying mechanisms through which additives control crystal morphology remain incompletely understood, and the application of additives for this purpose is still in the trial-and-error phase. This review discusses the mechanism of two types of additives-polymer (mainly pharmaceutical excipients) and small molecule (including surfactants and tailor-made additives)-on drug crystal morphology. These mechanisms include interfering with the attachment of solutes at the crystal-solution interface, altering the surface energy of crystals, and modifying solute-solvent interactions. By regulating the crystal growth process, these additives can effectively alter crystal morphology. This review also summarizes the application of these additives in solution crystallization, aiming to provide theoretical guidance for the use of additives in the modification of drug crystal morphology during crystallization processes.

     

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