流化床制粒数值模拟技术研究进展

Progress in numerical simulation technology for fluidized bed granulation

近年来,美国FDA大力倡导制药工业采用'质量源于设计(quality by design,QbD)'理念或建模与模拟技术来理解生产工艺。数值模拟技术因其经济性、科学性与直观性等优势,成为建模与模拟技术的主要工具之一,广泛应用于口服固体制剂混合、制粒、研磨、辊压、压片和包衣等多个系列单元操作。本文通过系统检索近20年的相关文献,对流化床制粒数值模拟技术的基本研究思路及其常用方法(离散元法、群体平衡模型、计算流体动力学)进行了总结,分别从气固流动、颗粒成形和颗粒干燥三方面综述了流化床制粒数值模拟技术研究进展。此外,提炼出当前研究存在的潜在问题及挑战,并对流化床制粒数值模拟技术的应用前景进行了展望。

In recent years,the adoption of the concept of'quality by design'(Qb D)or modeling and simulation technologies has been vigorously promoted in the pharmaceutical industry by Food and Drug Administration(FDA)for better understanding the manufacturing processes.Numerical simulation technology is one of the major tools for modeling and simulation owing to its advantages of economy,scientificity and intuition and has been widely used in the unit operations of solid oral dosage forms such as mixing,granulation,milling,rolling,tableting and coating.In this paper,the relevant literatures of nearly 20 years were systematically searched,and the basic principles and common methods(distinct element method,population balance model and computational fluid dynamics)of numerical simulation technology of fluidized bed granulation were summarized.Furthermore,the research progress in numerical simulation technology for fluidized bed granulation was reviewed from three aspects:gas-solid flow,particle agglomeration and drying.In addition,the potential problems and challenges in current research were pointed out,and the future perspectives of numerical simulation investigation of fluidized bed granulation were outlooked.