Experimental Evaluation of the Targeted Direct Design of Temperature Trajectories for Growth-Dominated Crystallization Processes Using an Analytical Crystal Size Distribution Estimator

The paper presents an experimental validation of a novel methodology for the systematic design of the set point operating curves for supersaturation-controlled, seeded crystallization processes, which produces a desired target crystal size distribution (CSD). The direct design approach is based on the idea of operating the system within the metastable zone (MSZ) bounded by the nucleation and the solubility curves. The proposed approach is based on an analytical CSD estimator, obtained by the analytical solution of the population balance equation for supersaturation-controlled growth-dominated processes. Based on the analytical estimator a design parameter for supersaturation-controlled processes is defined as a function of the supersaturation, time, and growth kinetics. Using the design parameter and the analytical CSD estimator, the temperature profiles in the time domain are determined to obtain a target distribution with a desired shape, while maintaining the constant supersaturation. The resulting temperature profile in the time domain can then be used as a set point for the temperature controller. This methodology provides a systematic targeted direct design approach for practical applications and scale-up. Experimental evaluations of two temperature trajectories designed with the proposed approach were carried out to achieve the desired target shape of the CSD. The experiments illustrate that the proposed targeted direct design approach can be used to systematically design different temperature trajectories and hence batch times, which lead to similar desired product CSD.