Regulation of Crystal\nHabit via Coupling “Growth\nDead Zone” and Temperature Cycling Strategy: Modeling and Validation

Temperature cycling, as a strategy to achieve crystal\nhabit regulation\nby taking advantage of the anisotropy of relative growth and dissolution\nrates, is preferred over chemical-based methods since it does not\nrequire further additional separation and purification steps; however,\nits long operating time and high energy consumption limit its application.\nTherefore, this work proposes a regulation strategy that couples temperature\ncycling with a “growth dead zone” and scales up the\ndimensionless-based morphological evolution model for guiding process\ndevelopment. This not only eliminates the negative effects of the\ngrowth dead zone, which not only reduces the product yield but also\nserves as an intensification tool that greatly improves the regulation\neffect. Specifically, a full-flow temperature cycling process design\nmodel is obtained from the initial to target morphology point according\nto the attainable region and evolution trajectories, and the introduction\nof empirical correction factor and dissolution degree effectively\nensures the model accuracy and process stability. Finally, the temperature\ncycling process of α-resorcinol in <i>n</i>-butanol\nwas chosen as an example for experimental validation, where the predicted\nresults obtained from the model can be in good agreement with experiments.