目的 研究组成、比例及制备工艺对欧前胡素-黄芩苷/葛根素共无定形系统（imperatorin-baicalin/puerarin co-amorphous system，Imp-Bai/Pue@CAS）形成和储存物理稳定性的影响。方法 采用偏光显微镜、X射线粉末衍射、差示扫描量热分析等方法对喷雾干燥法、旋转蒸发法和低温研磨法3种制备方法制备的不同比例的欧前胡素-黄芩苷样品和欧前胡素-葛根素样品进行物态表征；对室温，40℃及40℃、75%相对湿度3种储存条件下的CAS样品［Imp-Bai@CAS（1∶8、1∶10、1∶12）和Imp-Pue@CAS（1∶2、1∶3）］物态的动态变化进行物态表征；结合涂膜法和3种制备方法（喷雾干燥法、旋转蒸发法和低温研磨法）研究欧前胡素、黄芩苷和葛根素3种成分结晶趋势。结果 当欧前胡素和黄芩苷/葛根素组合时，物质的量比分别达到1∶8和1∶2，或更高比例的黄芩苷/葛根素、喷雾干燥条件下可形成共无定形系统（CAS），而旋转蒸发法和低温研磨法条件下未能形成CAS；欧前胡素-葛根素共无定形系统（Imp-Pue@CAS）的储存稳定性和葛根素比例呈正相关，而欧前胡素-黄芩苷1∶8共无定形系统［Imp-Bai@CAS（1∶8）］储存稳定性最佳；3种成分的结晶趋势为欧前胡素>黄芩苷>葛根素。结论 2种成分组合形成CAS时，结晶更慢的成分比例高有利于CAS的形成；喷雾干燥工艺更易制成Imp-Bai/Pue@CAS；合适的比例有利于维持CAS的储存物理稳定性。

Objective To study effects of composition, proportion and preparation process on the formation and storage physical stability of imperatorin-baicalin/puerarin co-amorphous system (Imp-Bai/Pue@CAS). Methods Imperatorin-baicalin samples and imperatorin-puerarin samples with different proportions prepared by spray drying method, rotary evaporation method and low temperature grinding method were characterized by polarizing microscope, X-ray powder diffraction and differential scanning calorimetry. CAS samples[Imp-Bai@CAS (1:8, 1:10, 1:12) and Imp-Pue@CAS (1:2, 1:3)] were stored at room temperature, 40℃ and 40℃, 75% relative humidity, which were characterized by the dynamic change of the state. The crystallization trend of imperatorin, baicalin and puerarin was studied by coating method and three preparation methods (spray drying method, rotating evaporation method, low temperature grinding method). Results The molar ratios of imperatorin and baicalin/puerarin were 1:8 and 1:2, respectively. The co-amorphous system (CAS) could be formed under the conditions of spray drying, or higher proportion of baicalin/puerarin, while the CAS could not be formed under the conditions of rotary evaporation and low temperature grinding. The storage stability of imperatorin-puerarin co-amorphous system (Imp-Pue@CAS) was positively correlated with the proportion of puerarin, while imperatorin-baicalin 1:8 co-amorphous system[Imp-Bai@CAS (1:8)] had the best storage stability. The crystallization trends of the three components are as follows:imperatorin > baicalin > puerarin. Conclusion When the two components are combined to form CAS, the higher proportion of components with slower crystallization is beneficial to the formation of CAS. Spray drying process is easier to make Imp-Bai/Pue@CAS; An appropriate ratio is beneficial to maintain the storage physical stability of the CAS.

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）