高品质中药制剂“物料-工艺-装备”协同智能设计  

Intelligent co-design of material,process,and equipment for manufacturing high-quality traditional Chinese medicine preparations

作　　者：徐冰[1,2] 乔延江 杜守颖[1] 张志强 肖伟[4] XU Bing;QIAO Yan-jang;DU Shou-ying;ZHANG Zhi-qiang;XIAO Wei(School of Chinese Materia Medica,Bejing Unversity of Chinese Medicine,Bejing 102488,China;Bejing Key Laboratory for Production Process Control and Quality Evaluation of Chinese Medicine,Bejing Municipal Science&Technology Commission,Beijing 102488,China;National and Regional Joint Engineering Research Center for Key Technologies of Chinese Medicine Formula Granules,Tianjin 301700,China;National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture,Lianyungang 222001,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京市科委中药生产过程控制与质量评价北京市重点实验室,北京102488 [3]中药配方颗粒关键技术国家地方联合工程研究中心,天津301700 [4]中药制药过程控制与智能制造技术全国重点实验室,江苏连云港222001

出　　处：《中国中药杂志》2023年第15期3977-3987,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82074033);连云港市重大技术攻关“揭榜挂帅”项目(CGJBGS2101);中国工程院战略研究与咨询项目(2022-XY-44);中国药品监管科学行动计划第二批重点项目。

摘　　要：在制药4.0(Pharma 4.0)的背景下,支撑药品质量源于设计(QbD)的设计工具加速朝向智能设计方向迭代。该文针对常规中药制剂研发多依赖经验、设计实验参数维度有限、工艺装备匹配度低,以及工艺放大试错成本高等局限,提出“物料-工艺-装备”协同智能设计解决方案,以中药口服固体制剂(OSD)为例,从设计模式、设计目标、设计工具和设计应用4个方面进行了介绍。在设计模式中,提出由关键物料属性、关键工艺参数、关键设备属性和关键质量属性构成的制剂设计四面体。通过市售药品评价,提出基于产品质量属性分类的高品质中药制剂设计目标。在设计工具中,描述了iTCM粉体物性数据库、工艺分类系统、系统建模与仿真,以及可靠性优化设计等中药制剂智能设计平台关键组件,以及不同平台模块在中药OSD共性关键环节规律性设计知识高效获取中的作用。最后,以中药高剪切湿法制粒工艺设计和中药配方颗粒溶化性设计为例,介绍了“物料-工艺-装备”协同智能设计应用。开展先进制剂设计理论与方法研究,将有助于提高中药制剂研发效率、可靠性和产品品质,推动中药高端制剂产品引领创新。In the context of Pharma 4.0,the design tools that support the pharmaceutical Quality by Design(QbD)are iterating fast toward intelligent or smart design.The conventional development methods for traditional Chinese medicine(TCM)preparations have the limitations such as over dependence on experience,low dimensions for the designed experiment parameters,poor compatibility between the process and equipment,and high trial-and-error cost during process scale-up.Therefore,this paper innovatively proposed the intelligent co-design involving material,process,and equipment for manufacturing high-quality TCM preparations,and introduced the design philosophy,targets,tools,and applications with TCM oral solid dosage(OSD)as an example.In terms of design philosophy,the pharmaceutical design tetrahedron composed of critical material attributes,critical process parameters,critical equipment attributes,and critical quality attributes was developed.The design targets were put forward based on the product performance classification system.The design tools involve a design platform that contains several modules,such a as the iTCM material database,the processing route classification system,the system modeling and simulation,and reliability-based optimization.The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced.At last,the applications of the co-design methodology involving material,process,and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated.The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development,improve the product quality,and promote the innovation of high-end TCM products across the industry.

关 键 词：质量源于智能设计 制剂设计四面体 物性数据库 制造分类系统 系统建模与仿真 可靠性优化 

分 类 号：R283[医药卫生—中药学]