基于QbD理念的微晶纤维素高速剪切湿法制粒过程实验研究

发布时间：2019-03-12 21:18

【摘要】：本文应用质量源于设计(quality by design,Qb D)方法,建立高速剪切湿法制粒过程设计空间并验证。本研究以微晶纤维素(microcrystalline cellulose,MCC)-去离子水体系为载体,颗粒中值粒径和松装密度为关键质量属性,采用Plackeet-Burmann设计对干混时间、干混搅拌桨、切割刀转速、水用量、水加入时间、湿混时间、湿混搅拌桨、切割刀转速和干燥时间进行筛选,中心点复合设计对筛选出的关键工艺参数进行优化,并基于二次多项式回归模型开发过程设计空间。方差分析结果显示回归模型的P值均小于0.05,且失拟值均大于0.1,表明该模型可较好的描述关键质量属性和关键工艺参数之间的关系。设计空间以Overlay plot展示,加入95%置信区间后,可缩小设计空间范围并提高其可靠性,设计空间内的颗粒粒径可控制在250~355μm,颗粒松装密度可控制在0.4~0.6 g·cm-3。结果显示,基于Qb D理念建立高速剪切湿法制粒过程设计空间,可以提高工艺过程的稳健性和灵活性。
[Abstract]:In this paper, the design space of high-speed shear wet granulation process is established and verified by mass derived design (quality by design,Qb-D) method. In this study, microcrystalline cellulose (microcrystalline cellulose,MCC)-deionized water system as carrier, the median particle size and bulk density as the key quality attributes, Plackeet-Burmann design for dry mixing time, dry mixing paddle, cutting knife speed, water consumption, Water adding time, wet mixing propeller, cutting cutter rotation speed and drying time were selected. The key process parameters were optimized by central point composite design, and the design space was developed based on quadratic polynomial regression model. The results of ANOVA show that the P value of the regression model is less than 0.05, and the misfitting value is more than 0.1, which indicates that the model can better describe the relationship between the key quality attributes and the key process parameters. The design space is displayed by Overlay plot. After adding 95% confidence interval, the scope of the design space can be reduced and the reliability can be improved. The particle size in the design space can be controlled in the range of 250 ~ 355渭 m, and the loose loading density of the particle can be controlled in the range of 0.4 脳 0.6 g / cm-3.. The results show that the design space of high-speed shear wet granulation process based on Qb-D concept can improve the robustness and flexibility of the process.
【作者单位】：北京中医药大学中药信息工程研究中心;教育部中药制药与新药开发关键技术工程研究中心;
【基金】：国家自然科学基金资助项目(81403112) 北京市重点实验室建设项目(中药基础与新药研究实验室,2014) 北京市自然科学基金项目(7154217) 北京中医药大学优秀青年教师骨干专项(2014-QNJSZX011)
【分类号】：R943

【参考文献】