(285c) Optimization of Batch and Continuous Cooling Crystallization of High Aspect Ratio Crystals Under Nucleation, Growth, Dissolution and Breakage for Shape Control

Authors: 
Acevedo, D., Purdue University
Burcham, C. L., Eli Lilly and Company
Jarmer, D., Eli Lilly & Company
Nagy, Z. K., Purdue University

Batch and continuous cooling crystallization of potassium dihydrogen phosphate in an impure media is evaluated through the implementation of various optimization frameworks to assess the achievable crystal size and shape. The continuous system studied is a two-stage mixed-suspension mixed-product removal (MSMPR) crystallization process. The systems are modelled using a multi-dimensional population balance model under nucleation, growth, and dissolution kinetics. The impact of agitation rate is studied by considering a binary crystal breakage model. A significant decrease in the achievable aspect ratio is observed by controlling the dissolution of crystals (batch scenario) and limiting the residence time and growth (continuous scenario). Further improvement of the final shape is achieved by considering the agitation rate in the optimization framework. However, the increase in the variance of the crystal mean size and aspect ratio indicates a trade-off between the aspect ratio and spread of the crystal size distribution. Nonetheless, this work illustrates promising results for further development of process optimization frameworks and control approaches for batch or continuous cooling crystallization operations by considering multiple crystallization kinetics and binary crystal breakage kernels, which can be used as a generic model-based design framework for batch and continuous crystallization processes of needle shaped particles to achieve desired mean aspect ratio.