目的 基于"质量源于设计"（quality by design，QbD）理念，采用设计空间法优化参蒲盆炎颗粒喷雾干燥工艺。方法 首先将集粉率、水分含量及芍药苷、绿原酸、虎杖苷、丹酚酸B含量6个指标作为关键质量属性（critical quality attribute，CQA），采用Plackett-Burman（P-B）设计实验，通过加权标准偏回归系数筛选出进风温度、进样速率、药液密度为3个关键工艺参数（critical process parameter，CPP）；再采用Box-Behnken设计实验，通过逐步回归法建立CQA和CPP间的数学模型。结果 方差分析显示模型P值均小于0.05，失拟值均大于0.05，可以较好地描述CQA和CPP之间的关系。最后通过Monte Carlo仿真法计算获得基于概率的设计空间并验证。结论 在工艺参数设计空间内操作能够保证参蒲盆炎颗粒喷雾干燥工艺品质稳定，有助于提高批次间质量均一性，为产业化提供数据支撑。

Design space approach was applied to optimize the spray drying process of Shenpu Penyan Granule (SPG) based on the concept of quality by design (QbD). The yield, moisture content, the content of paeoniflorin, chlorogenic acid, polydatin and salvianolic acid B were defined as the process critical quality attributes (CQAs). Based on the Plackett-Burman design, three critical process parameters (CPPs) including inlet temperature, specific gravity, and feeding speed were identified by using the weighted standardized partial regression coefficient method. And stepwise regression method was then used to establish the mathematical model between CQAs and CPPs in the Box-Behnken design. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could describe the relationship between CQAs and CPPs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of SPG can be guaranteed by operating within the design space parameters, which helps to improve the quality uniformity between batches of phenol extracts and provides data support for industrialization production.

R283.6

国家“重大新药创制”科技专项“盆腔炎性疾病后遗症治疗药物参蒲盆炎颗粒的临床研究”（2017ZX09301035）