目的 制备葛根素-黄芩苷共无定形（puerarin-baicalin co-amorphous，Pue-Bai-CA）混合物系统，考察葛根素对无定形黄芩苷物理稳定性及其溶出的影响及其机制。方法 利用喷雾干燥法制备葛根素、黄芩苷、Pue-Bai-CA系统，采用偏振光显微镜（polarizing microscope，PLM）、差示扫描量热法（differential scanning calorimetry，DSC）、X射线单晶衍射法（X ray single crystal diffraction，XRD）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FT-IR）等表征其固态特征；按照《中国药典》2020年版溶出度测定法测定黄芩苷的溶出度；用相溶解度法研究葛根素对黄芩苷溶出度的影响；同时测定其吸湿性和储存稳定性。结果 喷雾干燥法能成功制备葛根素、黄芩苷无定形样品和Pue-Bai-CA样品，共无定形系统中2者存在明显的相互作用；Pue-Bai-CA系统中黄芩苷的溶出优于晶体混合物，晶体混合物优于黄芩苷无定形；相溶解度结果显示，黄芩苷与葛根素形成了1∶1 A_L型络合物；Pue-Bai-CA系统的物理稳定性优于黄芩苷无定形。结论 Pue-Bai-CA系统可提高黄芩苷无定形的物理稳定性和溶出度，其机制与提高玻璃化转变温度（glass transition temperature，T_g）、2者之间存在相互作用及形成络合物有关。

Objective The mixture system of puerarin-baicalin co-amorphous(Pue-Bai-CA) was prepared to investigate the effect of puerarin on the physical stability and dissolution of amorphous baicalin and its mechanism. Methods Puerarin, baicalin and Pue-Bai-CA systems were prepared by spray drying method, and their solid state characteristics were characterized by polarized light microscopy (PLM), differential scanning calorimetry (DSC), X ray single crystal diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The dissolution rate of baicalin was determined according to the dissolution rate determination method of Chinese Pharmacopoeia (2020 edition). The effect of puerarin on the dissolution of baicalin was studied by phase solubility method. Its hygroscopicity and storage stability were also measured. Results The amorphous samples of puerarin amorphous, baicalin amorphous samples, and Pue-Bai-CA sample were successfully prepared by spray drying method, and there was obvious interaction between the two in the amorphous system. The dissolution of the co-amorphous system baicalin is better than that of the crystal mixture, which is better than that of the amorphous system baicalin. The phase solubility results showed that baicalin and puerarin formed 1:1 A_L complex. The physical stability of co-amorphous system is better than that of baicalin amorphous system. Conclusion Co-amorphous can improve the physical stability and dissolution of baicalin amorphous, and the mechanism is related to the increase of T_g, the interaction between the two and the formation of complex.

国家自然科学基金资助项目(82160751);江西中医药大学中药制剂技术与制药装备创新团队(CXTD22006);校级大学生创新创业计划项目(202110412212)