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.

R283.6

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）