中药质量源于设计方法和应用：工艺建模(1)
摘要 藥品质量源于设计(Quality by Design，QbD)强调对制药过程的透彻理解，即理解原料、工艺和产品质量之间的多维组合和相互作用关系。数学模型以函数关系的形式表征所研究工艺系统或过程“输入-输出”量对的集合，是解释制药质量传递规律，实现产品关键质量属性(CQAs)预测的重要工具。本文提出依据数学模型对终产品质量的影响程度将工艺模型分为高、中、低3类。为规范建模过程、提高建模效率，提出工艺建模质量管理规范(GMoP)。总结了机理建模、统计建模和混合建模方法，并介绍了数学模型在中药提取、干燥、制粒、粉体压缩、制药过程质量监控和工艺系统表征中的应用。
关键词 质量源于设计;中药;系统建模;质量传递规律;质量预测
Chinese Medicine Quality Derived From Design Methods and Applications for-(Ⅲ)：Process Modeling
, http://www.100md.com
Shi Guolin1， Xu Bing1，2， 3， Lin Zhaozhou4， 5， Shi Xinyuan1，2，3， Dai Xingxing1， Qiao Yanjiang1， 2， 3
(1 Department of Chinese Medicine Information Science， Beijing University of Chinese Medicine， Beijing 102400， China; 2 Beijing
Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine， Beijing Municipal
Science &Technology Commission， Beijing 100029， China; 3 Engineering Research Center of Key Technologies for Chinese
, 百拇医药
Medicine Production and New Drug Development， Ministry of Education of People′s Republic of China， Beijing 100029，China; 4 Beijing Traditional Chinese Medicine Hospital， Capital Medical University， Beijing 100010， China;
5 Institute of clinical pharmacy， Beijing Municipal Health Bureau， Beijing 100035， China)
Abstract Pharmaceutical Quality by Design (QbD) emphasizes comprehensive understandings of multidimensional combinations and interactions among raw materials， process and product quality during the pharmaceutical manufacturing processes. Such understandings could be realized by mathematical models， which characterize the “input-output” relationships of process systems and are important tools for explaining the laws of pharmaceutical quality transfer and predicting final product critical quality attributes (CQAs). Based on the quality risk management principles and the influence of mathematical models on the final product quality， process models were divided into high， medium and low risk categories. And good modeling practice (GMoP) was introduced to standardize the modeling process and to improve the efficiency of process modeling. This paper also summarized the methods of mechanistic model， statistical model and hybrid model， and reviews the applications of mathematical models to the extraction， drying， granulation， powder compression， process monitoring and control， and application of process system characterization.
Key Words Quality by Design (QbD); Chinese medicine; System modeling; Quality transfer rules; Quality prediction, 百拇医药(石国琳 徐冰 林兆洲 史新元 戴幸星 乔延江)
关键词 质量源于设计;中药;系统建模;质量传递规律;质量预测
Chinese Medicine Quality Derived From Design Methods and Applications for-(Ⅲ)：Process Modeling
, http://www.100md.com
Shi Guolin1， Xu Bing1，2， 3， Lin Zhaozhou4， 5， Shi Xinyuan1，2，3， Dai Xingxing1， Qiao Yanjiang1， 2， 3
(1 Department of Chinese Medicine Information Science， Beijing University of Chinese Medicine， Beijing 102400， China; 2 Beijing
Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine， Beijing Municipal
Science &Technology Commission， Beijing 100029， China; 3 Engineering Research Center of Key Technologies for Chinese
, 百拇医药
Medicine Production and New Drug Development， Ministry of Education of People′s Republic of China， Beijing 100029，China; 4 Beijing Traditional Chinese Medicine Hospital， Capital Medical University， Beijing 100010， China;
5 Institute of clinical pharmacy， Beijing Municipal Health Bureau， Beijing 100035， China)
Abstract Pharmaceutical Quality by Design (QbD) emphasizes comprehensive understandings of multidimensional combinations and interactions among raw materials， process and product quality during the pharmaceutical manufacturing processes. Such understandings could be realized by mathematical models， which characterize the “input-output” relationships of process systems and are important tools for explaining the laws of pharmaceutical quality transfer and predicting final product critical quality attributes (CQAs). Based on the quality risk management principles and the influence of mathematical models on the final product quality， process models were divided into high， medium and low risk categories. And good modeling practice (GMoP) was introduced to standardize the modeling process and to improve the efficiency of process modeling. This paper also summarized the methods of mechanistic model， statistical model and hybrid model， and reviews the applications of mathematical models to the extraction， drying， granulation， powder compression， process monitoring and control， and application of process system characterization.
Key Words Quality by Design (QbD); Chinese medicine; System modeling; Quality transfer rules; Quality prediction, 百拇医药(石国琳 徐冰 林兆洲 史新元 戴幸星 乔延江)