基于质量源于设计理念和信息熵赋值法优化陈皮配方颗粒喷雾干燥工艺  

Optimization of spray drying process for Citri Reticulatae Pericarpium formula granules based on quality by design concept andinformation entropy assignment method

作　　者：施文婷 刘远俊 张兰兰 林荣楷 刘权震 黄森 刘燎原 SHI Wenting;LIU Yuanjun;ZHANG Lanlan;LIN Rongkai;LIU Quanzhen;HUANG Sen;LIU Liaoyuan(Guangdong Yifang Pharmaceutical Co.,Ltd.Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Formula Granule,Foshan 528244,China)

机构地区：[1]广东一方制药有限公司、广东省中药配方颗粒企业重点实验室,佛山528244

出　　处：《环球中医药》2023年第11期2207-2214,共8页Global Traditional Chinese Medicine

基　　金：国家工业和信息化部2019年产业技术基础公共服务平台项目(2019-00902-1-2);佛山市应急科技攻关专项(2020001000206)。

摘　　要：目的应用质量源于设计理念,建立陈皮配方颗粒喷雾干燥工艺的设计空间并进行验证。方法将浸膏粉的得粉率及芸香柚皮苷、橙皮苷、川陈皮素和橘皮素含量作为关键质量属性,通过信息熵赋值法确定各质量指标的权重系数,并计算综合评分。采用Plackett-Burman试验设计对进风温度、雾化压力、药液温度、进料速度和药液相对密度进行筛选,运用中心点复合设计试验对筛选出的关键工艺参数进行优化,建立工艺设计空间,并选取6个试验点检验模型的预测能力。结果Plackett-Burman试验设计确定了药液相对密度和进料速度为关键工艺参数;中心点复合设计试验方差分析结果显示构建的模型可较好描述关键质量属性和关键工艺参数之间的关系(P<0.01);构建的关键工艺参数优化设计空间为药液相对密度1.04~1.05,进料速度18%~32%。结论在工艺参数设计空间内生产能够保证陈皮配方颗粒品质稳定,利于提高批次间质量均一性,为产业化提供数据支持。Objective To apply the concept of quality by design to establish and verify the design space of spray drying process for Citri Reticulatae Pericarpium formula granules.Methods The powder yield of extract powder and the contents of narirutin,hesperidin,nobiletin and tangeretin were taken as key quality attributes.The weight coefficient of each quality index was determined by the information entropy assignment method,and the comprehensive score was calculated.The Plackett-Burman experimental design was used to determine the air inlet temperature,atomization pressure.The temperature of the liquid medicine,the feeding speed and the relative density of the liquid medicine were screened,and the key process parameters screened out were optimized by the central composite design experiment.The process design space was established,and 6 test points were selected to test the predictive ability of the established model.Results The Plackett-Burman experimental design determined that the relative density of the liquid and the feed rate were the key process parameters;the results of the variance analysis of the central composite design experiment showed that the constructed model could well describe the relationship between the key quality attributes and the key process parameters(P<0.01).The optimal design space of the constructed the key process parameters is the relative density of liquid medicine 1.04~1.05,and the feeding rate is 18%~32%.Conclusion Production within the design space of process parameters can ensure the stable quality of the spray drying process of Citri Reticulatae Pericarpium formula granules,help to improve the quality uniformity between batches,and provide data support for industrialization.

关 键 词：质量源于设计 陈皮配方颗粒 喷雾干燥 信息熵赋值法 Plackett-Burman试验设计 中心点复合设计 

分 类 号：R283[医药卫生—中药学]