基于质量源于设计理念优化柳叶蜡梅挥发油包合物制备工艺

Optimization of the preparation process of volatile oil inclusion compound of Chimonanthus salicifolius S.Y.Hu based on quality by design concept

目的:基于质量源于设计(QbD)理念优化柳叶蜡梅挥发油包合物制备工艺。方法:以挥发油包合物的收率和包合率为关键质量属性(CQAs),选取了7个高风险因素设计Plackett-Burman试验,筛选出关键工艺参数;采用Box-Behnken试验设计分析CQAs与关键工艺参数的相关性;构建设计空间,选取最优操作空间。同时利用显微镜对包合物进行物理表征。结果:柳叶蜡梅挥发油包合物制备工艺优化出的操作空间为包合时间2.6~3.0 h,包合温度41~44℃,投料比(β-环糊精∶挥发油)7.7∶1~8.3∶1。该操作空间下包合物的收率>56%,包合率>73%,包合物形态均一稳定。结论:该包合工艺操作空间可行,为柳叶蜡梅挥发油包合物制备工艺的质量控制提供参考。

Objective:Optimize the preparation process of volatile oil inclusion compound of Chimonanthus salicifolius S.Y.Hu based on the concept of quality by design(QbD).Methods:The yield and inclusion rate of the volatile oil inclusion compound were selected as critical quality attributes(CQAs).Plackett-Burman experimental design was carried out to screen the investigation factors as the critical process parameters(CPPs).The correlation between CQAs and CPPs was analyzed by Box-Behnken experimental design.Then,the design space was constructed,and the optimal operation space was selected.Meanwhile,the inclusion compound was physically characterized using microscopy.Results:The operation space optimized for the preparation process of Chimonanthus salicifolius S.Y.Hu volatile oil inclusion compound was the inclusion time 2.6-3.0 h;the inclusion temperature was 41-44℃;the material ratio(β-cyclodextrin:volatile oil)was 7.7:1~8.3:1.The yield of the inclusion compound at this operating space was>56%,and the inclusion ratio was>73%.The morphology of the inclusion compound was homogeneous and stable.Conclusion:The inclusion process is feasible in operation space,and it provides a reference for the quality control of the preparation process of volatile oil inclusion of Chimonanthus salicifolius S.Y.Hu.