Simultaneous Parameter Estimation and Optimization of a Seeded Antisolvent Crystallization

Abstract

A population balance incorporating nucleation, growth, and agglomeration, solved using quadrature method of moments, was coupled with a parameter estimation procedure. The seeded antisolvent crystallization of paracetamol from methanol and water was chosen as the model system. All parameters concerned were regressed from moments calculated using the measured square weighted chord length distribution (CLD) generated by focused beam reflectance measurements (FBRM). The FBRM and the concentration data are utilized together to obtain experimental moments that reflect the mass of solids in the tank. Using the estimated kinetic parameters, the crystallization model was validated using an additional experiment with a new nonlinear addition rate. Experimental crystal size distributions (CSDs) measured by laser diffraction were compared to CSDs calculated by the model and were found to be in good agreement. No such work exists in the literature using FBRM to model an antisolvent system which considers agglomeration. On the basis of the kinetic parameters estimated using the above method, the solution to the optimal antisolvent addition rate profiles was obtained by applying nonlinear constrained multiobjective free final time formulation optimization on the validated model. These profiles were experimentally tested and CSD were compared with experiments used in the parameter estimation procedure. A 73.3% reduction in batch time was achieved with little impact on the CSD. Analyses of the various conflictions are presented with the aid of a pareto optimal plot to provide the practitioner with increased flexibility.