Chapter 7 - Advanced multiphase hybrid model development of fluidized bed wet granulation processes

Abstract

Abstract In pharmaceutical manufacturing, fluidized bed granulation is one of the common processing options available to achieve better flowability of powders through size enlargement of primary particles. In fact over the last 50 years, various fluidized bed operations, including freezing, drying, impregnation, coating, etc., have become a common place in the chemical processing industry due to the high level of contacts between fluids and solids attainable in a fluid bed system. These complex interactions between the fluid and particles also mean that simulating fluidized beds are still a challenging endeavor. In general, computational fluid dynamics (CFD) packages are employed to model the pressure drops in fluids; however, the presence of high concentration of solids and the complexity of granulation behavior require more advanced particle models than are available with CFD software. As a result, hybrid frameworks that utilize the strength of particulate simulations such as discrete element method (DEM) and bulk granulation modeling such as population balance model (PBM) in conjunction with CFD information are the next steps to developing practical fluid bed granulation models. This chapter aims to provide a comprehensive description of the development, implementation, and application of advanced modeling techniques for particulate processes occurring during wet granulation in a top-spray fluid bed unit operation. The presented framework demonstrates a practical process model development methodology by efficiently coupling multiphase simulation techniques (CFD-DEM-PBM), which can be used for effective process design, development, and scale-up purposes.