基于QbD理念的青钱柳复方提取液喷雾干燥工艺的优化实验

Optimization of spray drying parameters for cyclocaryapaliurus compound extract using a quality by design approach

目的:建立青钱柳复方提取液喷雾干燥工艺的设计空间。方法:以浸膏粉得粉率、浸膏粉含水量、浸膏粉多糖含量为关键质量属性(critical quality attribute,CQA),采用Plackeet-Burmann因子筛选实验方法设计对进风温度、进料速度、雾化压力、药液相对密度和药液温度进行筛选,采用Central-Composite中心复合设计对筛选出的关键工艺参数(critical process parameter,CPP)进行优化,在二次多项式回归模型的基础上建立青钱柳复方提取液喷雾干燥工艺设计空间,并加以验证。结果:方差分析结果显示所有模型(P<0.05),失拟项(P>0.05),表明该模型可以较好描述CQA和CPP之间的关系。设计空间以Overlay plot方式展示,并加入95%置信区间,可提高设计空间工艺过程的稳定性和可靠性。结论:基于质量源于设计(QbD)理念建立的青钱柳复方提取液喷雾干燥工艺设计空间,可提高其工艺的稳健性,降低产品质量可变性。

Objective： To establish the design space of spray drying process of cyclocaryapaliurus compound extract. Methods： The powder yield,moisture content and polysaccharide content of the extract powder were identified as the critical quality attributes（ CQAs）. Plackeet-Burmann experimental design was used to screen the following factors： inlet temperature,pump speed,spray pressure,relative density and liquid temperature,and the optimization was implemented with the Central-Composite experimental design based on screened critical process parameters（ CPPs）. The design space of spray drying process of cyclocaryapaliurus compound extract was established based on the quadratic polynomial regression model,and further validated by experiments. Results： Since the P-values of all models were less than 0. 05 and P-values of items lack of fit were more than 0. 05,the relationship between CQAs and CPPs could be well described by the three models. The stability and reliability of the design space,as illustrated by the Overlay plot with the addition of 95% confidence interval,was improved. Conclusion：The robustness of spray drying process of cyclocaryapaliurus compound extract process can be enhanced and the variability of product quality can be reduced via the establishment of design space based on quality by design（ QbD） concept.