Manipulation of Particle Morphology by Crystallization, Milling, and Heating Cycles—A Mathematical Modeling Approach

A new process consisting of a combination of crystallization, milling, and dissolution stages is presented. At first, a mathematical model for the different unit operations, as well as their coupling, is developed, based on the basic phenomena characterizing the evolution of the ensemble of particles in terms of both size and shape. Because of the broad design space and the plethora of interparticle phenomena, the mathematical model stands out as a vital tool for an in silico assessment of process feasibility. Subsequently, computer simulations can be exploited for a thorough understanding of the effect of the different operating conditions. The results collected are discussed considering the particle size and shape distribution in its entirety and by means of its properties, such as the average sizes and the variance. A final assessment is performed by comparing the combined process with a single cooling crystallization stage, both with and without a milling of the final products.