基于质量源于设计理念的调脂柔脉颗粒制备工艺研究  

Research on the Preparation Process of Tiaozhi Roumai Granules Based on Quality by Design Concept

作　　者：曹旸 张颖[2] 赵小梅 屈琼 赵佩媛 张新博 杨志宏 段玺 CAO Yang;ZHANG Ying;ZHAO Xiaomei;QU Qiong;ZHAO Peiyuan;ZHANG Xinbo;YANG Zhihong;DUAN Xi(Affiliated Hospital of Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China;Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712046,China)

机构地区：[1]陕西中医药大学附属医院,陕西咸阳712000 [2]陕西中医药大学,陕西咸阳712046

出　　处：《陕西中医药大学学报》2023年第5期60-70,共11页Journal of Shaanxi University of Chinese Medicine

基　　金：陕西中医药大学附属医院科研项目(2020ZJ007);国家重点研发计划项目(2019YFC1711204);陕西省教育厅项目(21JC011);陕西省中医药管理局项目(2021-04-ZZ-007);国家中医药管理局中药制剂三级实验室项目(1008);陕西省中药基础与新药研究重点实验室项目(1008);陕西省中药制药重点学科专项资助项目(1008)。

摘　　要：目的基于质量源于设计(Quality by Design,QbD)理念优化调脂柔脉颗粒的处方配比及制备工艺并建立其有效成分的含量测定方法。方法通过单因素试验确定最佳处方组成,结合鱼骨图以及失效模式及效应分析(Failure mode and effect analysis,FMEA)确定调脂柔脉颗粒制备过程中的关键工艺参数(Critical process parameters,CPPs)和关键质量属性(Critical quality attributes,CQAs),采用Box-Behnken响应面法进一步优化制备工艺并利用HPLC法测定调脂柔脉颗粒中大黄酚、丹酚酸A两种成分的含量。结果最佳润湿剂为70%乙醇,最佳填充剂为α-乳糖与糊精按1∶2合用,最佳处方比例为主药∶稀释剂∶黏合剂为4∶12∶5.5;最优条件下制备的调脂柔脉颗粒中大黄酚含量为0.716 mg·g^(-1),丹酚酸A的含量为0.525 mg·g^(-1),成型率大于82.23%,颗粒剂质量检查符合标准。结论基于QbD理念的调脂柔脉颗粒制备工艺稳定可行,质量稳定可控。Objective To optimize the prescription ratio and preparation process of Tiaozhi Roumai granules based on the concept of Quality by Design(QbD),and establish a method for determining the content of its active ingredients.Methods The optimal prescription composition was determined through single factor experiments,and the critical process parameters(CPPs)and critical quality attributes(CQAs)during the preparation process of Tiaozhi Roumai granules were determined by combining fishbone diagrams and failure mode and effect analysis(FMEA),The preparation process was further optimized using Box Behnken response surface methodology and HPLC was used to determine the content of two components,chrysophanol and salvianolic acid A,in Tiaozhi Roumai granules.Results The best wetting agent is 70%ethanol,and the best filling agent isα-Lactose and dextrin are used in a ratio of 1∶2,with the optimal prescription ratio of main drug:diluent:adhesive being 4∶12∶5.5;The content of chrysophanol in Tiaozhi Roumai granules prepared under the optimal conditions is 0.716 mg·g^(-1),and the content of salvianolic acid A is 0.525 mg·g^(-1).The molding rate is greater than 82.23%,and the quality inspection of the granules meets the standards.Conclusion The preparation process of Tiaozhi Roumai granules based on the QbD concept is stable and feasible,and the quality is stable and controllable.

关 键 词：调脂柔脉颗粒 质量源于设计 Box-Behnken响应面法 制备工艺 关键工艺参数 

分 类 号：R283.6[医药卫生—中药学]