Modeling of Nucleation, Growth, and Dissolution of Paracetamol in Ethanol Solution for Unseeded Batch Cooling Crystallization with Temperature-Cycling Strategy

Controlling crystal size distributions is critical to ensure the quality of products and operational efficiency for downstream processing. In batch cooling crystallization, temper-ature cycling strategies are often employed to control the crystal size distribution and minimize fines. Optimizing the complex operation of this strategy, where crystallization and dissolution occur in a single batch run, remains a challenge. For this problem, we develop a model of the process by a population balance considering nucleation, growth, and dissolution of crystals. In a case study of paracetamol in ethanol, the parameters in the population balance model were estimated from multiple experimental runs. The developed model was validated against additional experimental data sets, where the concentration and crystal size distributions of the final crystal products were predicted successfully. R2 values are greater than 0.96 in all cases.