基于QbD理念优化救必应药材的炮制工艺

Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept

该研究基于质量源于设计(quality by design,QbD)理念,优化救必应药材炮制工艺。参考《中国药典》中救必应药材的炮制方法和成分要求,以紫丁香苷含量、长梗冬青苷含量、醇浸出物、碎片率和含水量为关键质量参数(critical quality attri-butes,CQAs),采用单因素考察确定浸泡时间、闷润时间和干燥时间为关键工艺参数(critical process parameters,CPPs),应用层次分析法(analytic hierachy process,AHP)-熵权法混合加权,确定CQAs的权重系数,计算综合评分;以综合评分为响应值,通过Box-Behnken试验设计建立CPPs和CQAs之间的数学模型,构建救必应药材炮制工艺的设计空间并验证。方差分析结果显示,数学模型的P<0.05,失拟值>0.05,R_(adj)~2=0.910 5,R_(pre)~2=0.831 0,表明所建模型具有统计学意义和良好的预测能力。结合生产因素,确定救必应药材炮制的最佳工艺为浸泡1 h,闷润4 h,切制成1 cm左右的片状,60~70℃鼓风干燥2 h。该研究优化所得的救必应药材炮制工艺稳定可行,可为救必应饮片的规范化制备及质量稳定提供参考。

Based on the concept of quality by design(QbD),this study optimized the processing technology of Ilicis Rotundae Cortex.According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia,the content of syringin and pedunculoside,alcohol extract,fragmentation rate,and moisture content were taken as the critical quality attributes(CQAs).The soaking time,moistening time,and drying time were taken as critical process parameters(CPPs) by single factor tests.The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method,and the comprehensive score was calculated.With the comprehensive score as the response value,Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs,and the design space for the processing of Ilicis Rotundae Cortex was built and verified.The results of ANOVA showed that the mathematical model had the P value below 0.05,the lack of fit greater than 0.05,adjusted R~2=0.910 5,and predicted R~2=0.831 0,which indicated that the proposed model had statistical significance and good prediction performance.Considering the factors in production,the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h,moistening for 4 h,and drying at 60-70 ℃ in a blast drier for 2 h.The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible,which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.