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该文在质量源于设计(QbD)理念的指导下,建立基于设计空间的银杏叶片高速剪切湿法制粒工艺控制策略,提高过程质量可控性和产品质量一致性。以颗粒中间体的中值粒径(D_(50))和松装密度(D_a)为关键质量属性(CQAs),采用失败模式和效应分析(FMEA)辨识潜在关键工艺参数(pCPPs)。采用Plackett-Burmann设计对潜在关键工艺参数进行筛选,确定黏合剂用量、湿混时间和湿混搅拌桨转速为关键工艺参数(CPPs)。在关键工艺参数范围内,采用Box-Behnken设计和二次多项式回归模型开发工艺设计空间。ANOVA分析显示回归模型的P<0.05,且失拟值>0.1,表明其可较好地定量描述CQAs和CPPs之间的关系。设计空间内任一CPPs组合均能分别将颗粒D_(50)和D_a控制在170~500μm和0.30~0.44 g·cm~(-3),进而满足银杏叶片机械性质要求。
Under the guidance of QbD concept, this paper establishes a control strategy based on design space of high-speed shear wet granulation process of Ginkgo biloba leaves to improve process quality control and consistency of product quality. Based on median particle size (D_ (50)) and bulk density (D_a) of granular intermediates, CQAs were used to identify potential key process parameters (pCPPs) using failure mode and effect analysis (FMEA). Plackett-Burmann design was used to screen the potential key process parameters to determine the amount of binder, wet mixing time and wet mixing speed as key process parameters (CPPs). Within the key process parameters, Box-Behnken design and quadratic polynomial regression models were used to develop the process design space. ANOVA analysis showed that the regression model of P <0.05, and the value of> 0.1, indicating that it can be a good quantitative description of the relationship between CQAs and CPPs. Any one CPPs combination in the design space can control the particle D_ (50) and D_a at 170 ~ 500μm and 0.30 ~ 0.44 g · cm ~ (-3) respectively, which can meet the mechanical properties of Ginkgo biloba leaves.