Regulation of Crystal Habit via Coupling “Growth Dead Zone” and Temperature Cycling Strategy: Modeling and Validation

Temperature cycling, as a strategy to achieve crystal habit regulation by taking advantage of the anisotropy of relative growth and dissolution rates, is preferred over chemical-based methods since it does not require further additional separation and purification steps; however, its long operating time and high energy consumption limit its application. Therefore, this work proposes a regulation strategy that couples temperature cycling with a “growth dead zone” and scales up the dimensionless-based morphological evolution model for guiding process development. This not only eliminates the negative effects of the growth dead zone, which not only reduces the product yield but also serves as an intensification tool that greatly improves the regulation effect. Specifically, a full-flow temperature cycling process design model is obtained from the initial to target morphology point according to the attainable region and evolution trajectories, and the introduction of empirical correction factor and dissolution degree effectively ensures the model accuracy and process stability. Finally, the temperature cycling process of α-resorcinol in n-butanol was chosen as an example for experimental validation, where the predicted results obtained from the model can be in good agreement with experiments.