Scale-up Modeling of a Pharmaceutical Crystallization Process via Compartmentalization Approach

In this work, a scale-up model of a pharmaceutical batch cooling crystallization process was developed. The model is based on a compartmentalization approach of a large-scale crystallizer. The compartmental properties (e.g. volume, location and flux connections) were extracted by using two different, manual and automatic zoning, strategies.

Each compartmentalization technique is based on a mixing study in the large-scale reactor with the help of computational fluid dynamics (CFD). The scale-up model was simulated in MATLAB/Simulink environment. The simulation results show the significant role of the fluid dynamics on the simulated process performance in terms of crystal size distribution and final average crystal diameter by means of comparing the multi-compartment model with a single-compartment well-mixed model.