少量添加剂改善葛根素-欧前胡素共无定形系统的溶出作用及其机制  

Improvement of dissolution behavior and mechanism of puerarin-imperatorin co-amorphous system by a small amount of additives

作　　者：欧阳琪 蒋且英 童雨 梁新丽 江和栋 廖正根 OUYANG Qi;JIANG Qieying;TONG Yu;LIANG Xinli;JIANG Hedong;LIAO Zhenggen(Ministry of Education Key Laboratory for Modern Preparations of Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Experimental Animal Science and Technology Center,Jiangxi University of Chinese Medicine,Nanchang 330004,China;College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]江西中医药大学实验动物科技中心,江西南昌330004 [3]江西中医药大学药学院,江西南昌330004

出　　处：《中草药》2024年第17期5785-5794,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82160751);江西中医药大学中药制剂传承创新与转化团队(CXTD22006)。

摘　　要：目的考察少量添加剂对葛根素-欧前胡素共无定形系统(puerarin-imperatorin co-amorphous system,Pue-Imp-CAS)溶出行为的改善作用及机制。方法利用芘荧光探针法考察葛根素、欧前胡素对十二烷基硫酸钠(sodium dodecyl sulfate,SDS)临界胶束浓度(critical micelle concentration,CMC)的影响;摇瓶法考察SDS、羟丙基甲基纤维素(hydroxypropyl methylcellulose,HPMC)、聚乙烯吡咯烷酮K30(polyvinylpyrrolidone K30,PVP-K30)对葛根素、欧前胡素平衡溶解度的影响;利用喷雾干燥法制备共无定形系统,采用X射线单晶衍射法(X-ray single crystal diffraction method,XRD)表征其固态特征;按照《中国药典》2020年版溶出度测定法测定葛根素、欧前胡素的溶出度;通过分散性实验评估样品的分散时间和结块程度;使用接触角测定仪器测量样品动/静态接触角,使用Lewis acid-bace(LW-AB)法与Young’s方程计算表面自由能。结果葛根素、欧前胡素对SDS的CMC无影响;少量SDS、HPMC、PVP-K30对葛根素、欧前胡素的晶体溶解度无影响;固态表征结果显示喷雾干燥产物为无定形;含少量添加剂的共无定形系统中葛根素、欧前胡素的溶出优于不含添加剂的共无定形系统,共无定形系统优于原料药及物理混合物,且不同添加剂的影响不同;含添加剂共无定形系统的接触角及分散时间均低于Pue-Imp-CAS。结论少量添加剂可改善Pue-Imp-CAS的溶出行为,其改善机制与添加剂改善系统的润湿性、添加剂及共无定形系统组成物的性质有关。Objective To study the improvement effect and mechanism of small amount of additives on the dissolution behavior of puerarin-imperatorin co-amorphous system(Pue-Imp-CAS).Methods The effects of puerarin and imperatorin on the critical micelle concentration(CMC)of sodium dodecyl sulfate(SDS)were investigated by pyrene fluorescent probe method,the effects of SDS,hydroxypropyl methylcellulose(HPMC)and polyvinylpyrrolidone K30(PVP-K30)on the equilibrium solubility of puerarin and imperatorin were investigated by shake flask method,the co-amorphous system was prepared by spray drying method,and its solid-state characteristics were characterized by X-ray single crystal diffraction(XRD).The dissolution of imperatorin,the dispersion time and the degree of agglomeration of the sample were evaluated by dispersion experiment,the dynamic/static contact angle of the sample was measured by the contact angle measuring instrument,and the surface free energy was calculated by the Lewis acid-bace(LW-AB)method and Young’s equation.Results Puerarin and imperatorin had no effect on the CMC of SDS,a small amount of SDS,HPMC and PVP-K30 had no effect on the crystal solubility of puerarin and imperatorin,the solid state characterization results showed that the spray-dried product was amorphous,puerarin and imperatorin in the co-amorphous system with a small amount of additives,The dissolution of puerarin and imperatorin was better than that of the co-amorphous system without additives,and the co-amorphous system was better than that of the active pharmaceutical ingredient(API)and physical mixture,and the effects of different additives were different,and the contact angle and dispersion time of the co-amorphous system with additives were lower than those of Pue-Imp-CAS.Conclusion A small amount of additives can improve the dissolution behavior of Pue-Imp-CAS,and the improvement mechanism is related to the wettability of the additive-improved system,the properties of the additives and the components of the amorphous system.

关 键 词：葛根素 欧前胡素 共无定形系统 临界胶束浓度 分散性 集聚率 解团聚 接触角 润湿性能 

分 类 号：R283.6[医药卫生—中药学]