处方优化对于生产工艺的影响final.pdf

处方对于生产工艺和可放大性的影响 处方对 生产 艺 放大性的影响 Effect of Formulation on Pharmaceutical Process and ScaleProcess and Scale-upup 杨东博士 扬子江药业集团药物研究院 Dong Yang, Ph.D. Institute of Pharmaceutical Research and Development, YangTzeYangTze RiverRiver PharmaceuticalPharmaceutical GroupsGroups 理想制剂产品的要求 Requirements of A Desired Solid Dosage Form Criteria Stage of development Good bioavailability * Early stage y y g Good stability * Early and later stage Good processability and scalability * Later stage TheThe simplesimple, thethe betterbetter EarlyEarly andand laterlater stagestage (1) no bridging needed between early FormulationFormulation andand processprocess lockinglocking asas stagge and later stagge formulations early as possible (2) more useful clinical and stability data for NDA filling ** EssentialEssential requirementrequirement forfor aa dosagedosage formform 可放大性和可生产性 Scalability and Manufacturability 定义定义 产品可以从小型的实验设备转移到中型设备和生产型大设 备并可以顺利生产的特性备并可以顺利生产的特性。 可生产性的要求 11. 具有稳定和可以接受的产率；具有稳定和可以接受的产率； 2. 具有适当的生产操作空间，设备运行条件的波动不会 影响产品的质量和产率； 3. 产品质量符合预定的质量标准； 可放大性和可生产性的影响因素 F t Aff ti S l bilit d M f t bilit Factors Affecting Scalability and Manufacturability Scalability and MManuffac