Kinetics Estimation and Single and Multi-Objective Optimization of a Seeded, Anti-Solvent, Isothermal Batch Crystallizer

Abstract

The nucleation and growth kinetic parameters of paracetamol in an isopropanol−water antisolvent batch crystallizer were estimated by nonlinear regression in terms of the moments of the crystal population density. The moments were calculated using the measured chord length distribution (CLD) generated by the FBRM. The measured supersaturation by ATR-FTIR spectroscopy was also used to calculate the nucleation and growth rates using power law correlations. Using the estimated kinetic parameters, the crystallization model based on the population and mass balance, was validated using the open-loop experimental particle size distribution and supersaturation results. Subsequently, the solution to the optimal antisolvent flow-rate profiles was obtained by applying nonlinear constrained single- and multiobjective optimization on the validated model. These profiles were implemented on the crystallizer and crystal-size distributions were compared with the open-loop experiments. The bimodality in the particle size distribution (PSD), which was present in the open-loop experiments, was either minimized or completely eliminated with the optimal profile policies. The results of the multiobjective optimization showed an improvement of 27.5 μm and 3% in the volume weighted mean size and yield, respectively, in comparison to the best results obtained from the open-loop experiments.