Fluid Dynamics and Granular Growth in High Shear Wet Granulation

Doctoral thesis, 2007

High shear wet granulation is a key step in the manufacturing of tablets in the pharmaceutical industry. From the pharmaceutical industry’s point of view, there is a desire for predictive quantitative process models to be able to make in-silico process and scale-up simulations, which would shorten and reduce the cost of technology transfer from laboratory scale to manufacturing scale in drug development. The primary objective of the thesis is to develop mathematical models for describing the high shear granulation process. Population balance models are found to describe granule coalescence and growth well and in this study, both one-dimensional and multi-dimensional population balances have been implemented. However, the applicability of the population balances is limited if the particle flow in the granulator is not known in detail. Thus, the secondary objective of the thesis focuses on Experimental Fluid Dynamics (EFD), i.e. to develop experimental techniques for measuring the powder flow pattern, and to model the flow using Computational Fluid Dynamics (CFD). In the one-dimensional population balance, the granule size distribution alone is modelled. By dividing the coalescence kernel into two factors, collision frequency and collision efficiency, respectively, it is found that the collision frequency expression derived from the assumption of equipartition of translational momentum between the colliding granules best describes the granulation process. In the multi-dimensional case, liquid saturation and porosity distributions for the granules are modelled as well. By generalizing the existing model, the temporal evolution of the distributions of particle size, liquid saturation and porosity can all be well modelled. Experimentally, a high speed camera is successfully used to obtain velocity data on the powder flow at the granulator wall and by using Laser Doppler Anemometry (LDA), the velocity field from the wall and up to 4 mm into the dense rotating powder mix can be measured. In the CFD flow simulations, the Kinetic Theory of Granular Flow combined with frictional stress models, is found to roughly describe the flow, and the experimentally found velocities act as validation of the flow model.