基于QbD理念应用混料设计法优化逍遥片的制备工艺  

Optimization of Preparation Process of Xiaoyao Tablets by Mixture Design Method Based on QbD Concept

作　　者：李慧婷 伍振峰[1,2] 张小飞 李远辉[1] 李延年[1] 刘恩位 李小锋 杨明 WU Zhen-feng;ZHANG Xiao-fei;LI Yuan-hui;LI Yan-nian;LIU En-wei;LI Xiao-feng;YANG Ming(Chengdu University of Traditional Chinese Medicine （TCM） , Chengdu 611137, China;Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of TCM, Nanchang 330004, China;Shaanxi University of Chinese Medicine, Xianyang 712000, China;Jiangxi Puzheng Pharmaceutical Co. Ltd. , Ji＇an 331409, China)

机构地区：[1]成都中医药大学,成都611137 [2]江西中医药大学现代中药制剂教育部重点实验室,南昌330004 [3]陕西中医药大学,陕西咸阳712000 [4]江西普正制药有限公司,江西吉安331409

出　　处：《中国实验方剂学杂志》2018年第15期36-42,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：江西省“赣鄱英才555”工程计划项目(赣组字[2012]95号)

摘　　要：目的：基于质量源于设计（QbD）理念优化逍遥片的处方配比及制备工艺。方法：采用湿法制粒压片法制备逍遥片。评估可能影响片剂质量的风险因素,采用Plackett-Burman设计筛选对评价指标有显著性影响的处方因素及工艺参数,以颗粒成型率、颗粒休止角、片剂外观及崩解时间为评价指标,通过混料设计法优化逍遥片的处方配比。结果：通过风险评估和Plackett-Burman试验确定了药辅比、填充剂中淀粉与乳糖的比例、崩解剂用量和润滑剂用量4个处方因素为影响实验结果的关键因素,通过混料设计建立的回归模型具有显著性意义,模型具有良好预测性,基于模型在最佳处方区域内选择的优化处方为逍遥片干浸膏粉-淀粉-乳糖-交联羧甲基纤维素钠-硬脂酸镁（73.2∶13.8∶10∶2∶1）,按此处方制备逍遥片,颗粒成型率、颗粒休止角、外观评分及崩解时间平均值分别为87.44%,34.97度,5分,32.3 min,平均综合评分为75.63分。结论：基于QbD理念及混料设计法对逍遥片的处方及工艺参数进行优化是可行的,所得的处方合理,工艺条件稳定,可为逍遥片的大生产提供参考。Objective： To optimize the formulation and preparation technology of Xiaoyao tablets based on quality by design（QbD）. Method： Xiaoyao tablets were prepared by wet granulation and granule compression.Firstly,the risk factors that may affect the quality of the tablets were evaluated. Plackett-Burman experimental design was used to screen the prescription factors and process parameters that had significant influence on the index. Taking formability of granules,angle of repose and appearance of tablets,disintegration time as evaluation indexes,the formulation of Xiaoyao tablets was optimized by mixture design. Result： By taking risk assessment and Plackett-Burman test,it was confirmed that the ratio of extract powder to excipients,the ratio of starch to lactose,the amount of disintegrant and lubricant were the key factors affecting the experimental results. The regression model established by the mixture design had significant significance and the model had good predictability. Based on the model,the optimal formulation was chosen within the optimal prescription area as dry extract powder-starch-lactose-croscarmellose sodium-magnesium stearate（73. 2 ∶ 13. 8 ∶ 10 ∶ 2 ∶ 1）. According to this prescription,Xiaoyao tablets was prepared,its average particle forming rate reached 87. 44%,the angle of repose was 34. 97°,the score of tablets＇ appearance was 5 points and the disintegration time was 32. 3 minutes, the comprehensive score reached 75. 63 points. Conclusion： It is feasible to optimize the prescription and process parameters of Xiaoyao tablets based on QbD concept and mixture design method. The prescription optimized by mixture design is reasonable, the process is stable and feasible, which can provide a reference for industrial production of Xiaoyao tablets.

关 键 词：质量源于设计 逍遥片 肝郁气滞 风险评估 混料设计 崩解时间 PLACKETT-BURMAN设计 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]