(130a) A Unified Framework for Mechanistic Model Development and Validation of High Shear, Fluid Bed, and Twin Screw Wet Granulation Processes

Particle size enlargement by wet granulation can be achieved through three types of processes: fluid bed, high shear, and twin screw granulation. Although these processes have many similarities, they differ at a mechanistic level. For instance, while fluid bed granulation is mainly driven by granule agglomeration and drying, the evolution of granules in a twin screw granulator is primarily governed by breakage and layering. As a result, each type of wet granulation process is defined by a unique set of critical process parameters, and the resulting granules have different properties depending on the means of production. Mechanistic modeling can be used to capture these differences and predict the effects of critical process parameters on granule attributes, facilitating process design and operation. In this work, a unified, mechanistic modeling framework is presented and customized for fluid bed, high shear, and twin screw granulation processes, taking into account the dominant mechanisms in each process and the spatial compartmentalization of the various equipment.

Once a mechanistic model has been developed, model validation poses a key challenge towards applying these tools in practice. These models consider multiple mechanisms that affect particle attributes, with each mechanism containing a number of unknown kinetic parameters. Because of their complex nature, the mechanisms are difficult to decouple experimentally, and the data requirements for model validation are not well-established. In this work, approaches to model validation are developed based on the mechanistic understanding of the relationships between critical process parameters and product attributes. Finally, case studies for model development and validation are presented for fluid bed and twin screw granulation processes.