Scale-up Modeling of a Pharmaceutical Antisolvent Crystallization via a Hybrid Method of Computational Fluid Dynamics and Compartmental Modeling

In this work, a model of a 218 L scale pharmaceutical antisolvent crystallization process was developed. The model is based on a hybrid method of computational fluid dynamics (CFD) and compartmental modeling. In the model, the mixing behaviour of the bulk fluid at two different impeller speeds was obtained from CFD simulations. The compartmental map of the crystallizer was extracted from CFD results based on a hypothesis driven compartmentalization approach. A novel dynamic compartment model was developed to capture the fluid dynamics during the feeding of the antisolvent into the crystallizer and implemented in MATLAB/Simulink environment. Developed model takes into account the changes in compartmental volume, solvent concentrations and density and it assumes a dynamic flow between compartments during the filling. Dynamic compartment model can be also applied in other areas of modeling practices in chemical engineering instead of steady-state compartment models such as fed batch fermentation.