基于QbD理念-亚临界水提技术制备北柴胡颗粒及其物理指纹图谱

Preparation and Physical Fingerprint of Bupleurum chinense Granules Based on QbD Concept and Subcritical Water Extraction Technology

基于质量源于设计(QbD)理念和亚临界水提技术,优化北柴胡颗粒的制备工艺,并采用物理指纹图谱法评价不同批次北柴胡颗粒的物理质量一致性。采用Box-Behnken响应面法优化亚临界加压热水提取工艺,再采用多指标综合加权法确定成型工艺参数。以休止角、豪斯纳比、水分、吸湿性、相对均齐度指数、松密度和振实密度为二级物理指标,建立物理指纹图谱。确定北柴胡颗粒的优化制备工艺参数为:料液比1∶14、提取时间40 min、提取温度131℃。采用湿法制粒,以微晶纤维素为填充剂,药辅比为1∶1,以90%乙醇为润湿剂,所得不同批次颗粒的物理指纹图谱相似度均大于0.99。优化的北柴胡颗粒制备工艺稳定、可行,提取效率高,所得颗粒物理质量稳定,为中药制剂研发提供了新思路。

Based on the quality by design(QbD)concept and subcritical water extraction technology,the preparation process of Bupleurum chinense granules was optimized,and the physical quality consistency of different batches of Bupleurum chinense granules was evaluated using the physical fingerprint method.The Box-Behnken designresponse surface method was adopted to optimize the subcritical hot water extraction technology.Multi-index comprehensive weighting method was used to determine the process parameters of molding.The physical fingerprint of granules was established with repose angle,Hausner ratio,moisture,hygroscopicity,relative homogeneity index,bulk density and tap density as the indexes.The optimized process parameters of Bupleurum chinense guanules were determined to be a solid-liquid ratio of 1∶14,extraction time of 40 min,and extraction temperature of 131℃.The final granules were prepared by wet granulation with microcrystalline cellulose as the filler,a drug to auxiliary ratio of 1∶1,and 90%ethanol as the humectant.The physical fingerprint similarity of different batches of the granules was higher than 0.99.The results indicated that the optimized preparation process of Bupleurum chinense guanules was stable and feasible,with high extraction efficiency,and the physical quality of the prepared granules was stable,which could provide new ideas for the research and development of traditional Chinese medicine preparations.