中药质量源于设计方法和应用：连续制造(1)
摘要 藥品质量源于设计(Quality by Design，QbD)鼓励采用创新制药工艺、技术和装备提高药品质量和生产效率。连续制造(Continuous Manufacturing)指在一段时间内不间断提供原料并生产出终产品的过程。与间歇(Batch)生产相比，连续制造具有占地面积少、生产周期缩短、智能化程度高、工艺易放大、产品质量一致性高等特点，符合未来药品生产发展趋势和需求。本文总结了连续制药过程关键技术和方法，包括连续喂料、连续混合、连续制粒等单元型连续制药过程，以及口服固体制剂、化学药合成和生物制品的全程型连续生产过程，介绍了停留时间分布分布(RTD)模型和过程分析技术(PAT)等先进控制方法在连续制药过程中的应用，以期对我国药品和中药生产的发展提供借鉴。
关键词 质量源于设计;中药;连续制造;停留时间分布模型;过程分析技术
Chinese Medicine Quality Derived From Design Methods and Applications for-(Ⅵ)：Continuous Manufacturing
, http://www.100md.com
Wang Fen1， Xu Bing1，2，3， Liu Yu4， Li Jianyu1， Shi Xinyuan1，2，3， 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
, http://www.100md.com
Medicine Production and New Drug Development， Ministry of Education of People′s Republic of China， Beijing 100029，China; 4 Joyea Co.， LTD.， Danyang 212300， China)
Abstract The pharmaceutical quality by design (QbD) encourages the use of innovative pharmaceutical technologies and equipment to improve drug quality and production efficiency. Continuous manufacturing refers to the process of supplying raw materials and producing the final product without interruption over a period of time. Compared with batch production， continuous manufacturing has the characteristics of less floor space， shorter production cycle， higher intelligence， easier process scale-up and higher product quality consistency， and meets the development trend and demand of drug production in the future. This paper summarizes the key technologies and methods of continuous pharmaceutical processes， including continuous feeding， continuous mixing， continuous wet granulation， and full-scale continuous production process of oral solid dosage preparations， chemical products and biological products. The applications of residence time distribution (RTD) model and process analytical technology (PAT) and other advanced control methods to the continuous pharmaceutical processes were also reviewed to provide references for the development and manufacturing of Chinese medicine preparations.
Key Words Quality by design; Chinese medicine; Continuous manufacturing; Residence time distribution model; Process analytical technology, http://www.100md.com(王芬 徐冰 刘雨 李建宇 史新元 乔延江)
关键词 质量源于设计;中药;连续制造;停留时间分布模型;过程分析技术
Chinese Medicine Quality Derived From Design Methods and Applications for-(Ⅵ)：Continuous Manufacturing
, http://www.100md.com
Wang Fen1， Xu Bing1，2，3， Liu Yu4， Li Jianyu1， Shi Xinyuan1，2，3， 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
, http://www.100md.com
Medicine Production and New Drug Development， Ministry of Education of People′s Republic of China， Beijing 100029，China; 4 Joyea Co.， LTD.， Danyang 212300， China)
Abstract The pharmaceutical quality by design (QbD) encourages the use of innovative pharmaceutical technologies and equipment to improve drug quality and production efficiency. Continuous manufacturing refers to the process of supplying raw materials and producing the final product without interruption over a period of time. Compared with batch production， continuous manufacturing has the characteristics of less floor space， shorter production cycle， higher intelligence， easier process scale-up and higher product quality consistency， and meets the development trend and demand of drug production in the future. This paper summarizes the key technologies and methods of continuous pharmaceutical processes， including continuous feeding， continuous mixing， continuous wet granulation， and full-scale continuous production process of oral solid dosage preparations， chemical products and biological products. The applications of residence time distribution (RTD) model and process analytical technology (PAT) and other advanced control methods to the continuous pharmaceutical processes were also reviewed to provide references for the development and manufacturing of Chinese medicine preparations.
Key Words Quality by design; Chinese medicine; Continuous manufacturing; Residence time distribution model; Process analytical technology, http://www.100md.com(王芬 徐冰 刘雨 李建宇 史新元 乔延江)