难溶性中药成分在过饱和体系下晶体成核和生长行为研究

目的研究难溶性中药成分在过饱和体系中的晶体成核和生长行为,为难溶性中药成分过饱和给药系统的设计奠定基础。方法通过反溶剂法制备载药过饱和体系,选择紫外-可见光谱法监测晶体成核和晶体生长过程,分别测定6种成分在较低过饱和度(S=5)和较高过饱和度(S=20)时的晶体成核诱导时间(tind)和晶体生长速度,利用偏振光显微镜(PLMC)、X射线衍射(XRD)、差示扫描量热仪(DSC)对沉淀进行表征。结果穿心莲内酯、延胡索乙素、丹皮酚、银杏内酯B、高饱和度的水飞蓟宾与姜黄素的成核诱导时间tind1 h,低过饱和度的水飞蓟宾与姜黄素的成核诱导时间tind1 h;穿心莲内酯与延胡索乙素在晶体生长过程中表现出负斜率,而水飞蓟宾、丹皮酚、姜黄素与银杏内酯B在则表现出正斜率。结论穿心莲内酯与延胡索乙素属于快速成核-快速晶体生长分子(I类);丹皮酚、银杏内酯B、较高过饱和度的水飞蓟宾与姜黄素属于快速成核-缓慢晶体生长分子(II类)、较低过饱和度的水飞蓟宾与姜黄素属于缓慢成核-缓慢晶体生长分子(IV类)。

Study on crystal nucleation and growth behavior of insoluble traditional Chinese medicine components in supersaturated system

Objective To study the crystal nucleation and growth behavior of insoluble traditional Chinese medicine components in supersaturated system, and lay the foundation for the design of insoluble traditional Chinese medicine supersaturated drug delivery system. Methods The drug-loaded supersaturated system was prepared by anti-solvent method, and the process of crystal nucleation and crystal growth was monitored by UV-vis spectroscopy. The nucleation induction time (t_ind) and crystal growth rate of six components were measured at low supersaturation and high supersaturation, respectively. The precipitation was characterized by polarized light microscope (PLMC), X ray diffraction (XRD), and differential scanning calorimeter (DSC). Results The nucleation induction time (t_ind) of andrographolide, tetrahydropalmatine, paeonol, ginkgolide B, silybin and curcumin with high saturation was less than 1 h, and the nucleation induction time of silybin and curcumin with low supersaturation was t_ind > 1 h. During crystal growth, andrographolide and tetrahydropalmatine showed negative slope, while silybin, paeonol, curcumin and ginkgolide B showed positive slope. Conclusion The andrographolide and tetrahydropalmatine belong to rapid nucleation-rapid crystal growth molecules (class I); Paeonol, ginkgolide B, higher supersaturated silybin and curcumin belong to fast nucleation-slow crystal growth molecules (class II), lower supersaturated silybin and curcumin belong to slow nucleation-slow crystal growth molecules (class IV).