Page 128 - 《中国药科大学学报》2025年第4期

学报
524 Journal of China Pharmaceutical University 2025, 56(4): 524 − 530

添加剂调控药物晶体形貌研究进展

任怡霏 ，苏 媛 ，蔡 挺 1,2,3*
2,3
1
1
（ 中国药科大学药学院, 南京 211198； 中国药科大学工学院, 南京 211198；
2
3 江苏省绿色制药与结晶关键技术工程研究中心, 南京 211198）
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。
关键词 晶体形貌；晶体生长；添加剂；溶液结晶；药物晶体
中图分类号 R944 文献标志码 A 文章编号 1000−5048(2025)04−0524−07
doi：10.11665/j.issn.1000−5048.2024081303

引用本文 任怡霏，苏媛，蔡挺. 添加剂调控药物晶体形貌研究进展 [J]. 中国药科大学学报，2025，56（4）：524 − 530.

Cite this article as: REN Yifei, SU Yuan, CAI Ting. Research progress on additives regulating drug crystal morphology[J]. J China Pharm
Univ, 2025, 56(4): 524 − 530.

Research progress on additives regulating drug crystal morphology
2,3
1
REN Yifei , SU Yuan , CAI Ting 1,2,3*
1 2
School of Pharmacy, China Pharmaceutical University, Nanjing 211198; School of Engineering, China Pharmaceutical
3
University, Nanjing 211198; Jiangsu Provincial Engineering Research Center for Key Green Pharmaceutical Manufacturing and
Crystallization Technologies, Nanjing 211198, China
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.
Key words crystal morphology; crystal growth; additives; solution crystallization; drug crystal

This study was supported by the National Natural Science Foundation of China(No. 82273880,No.22308384)

收稿日期 2024-08-13 * 通信作者 Tel：18305198179 E-mail：tcai@cpu.edu.cn
基金项目 国家自然科学基金项目（No.82273880，No.22308384）