Crystal Growth Kinetics of Benzoic Acid in Aqueous Ethanol Solution

Crystallization is one of the most important operations in the manufacturing of active pharmaceutical ingredients, where crystal growth is of vital importance for the final particle properties. The crystal growth kinetics of benzoic acid in antisolvent crystallization has been investigated by isothermal seeded desupersaturation experiments, applying the process analytical technology (PAT) tools and population balance modeling. The population balance equation (PBE) model selection incorporating different supersaturation expressions, growth rate expressions together with the solvent compositions was explored by fitting to corresponding concentration data sets. The results demonstrated that growth rate parameters depend heavily on solvent compositions. Therefore, a size-independent growth rate model concerning the effect of solvent compositions demonstrated the best fitness with respect to objective function values and confidence intervals. The estimated parameters with the corresponding model were consequently validated experimentally, demonstrating reasonable agreements with experimental concentrations, which illustrates the potential of the developed model in further experimental design and control.