(667a) A Population Balance Model Based Distribution Shaping Control for Tailored Dissolution of Crystalline Products

A novel methodology for the dynamic optimization of the crystal size distribution (CSD) considering growth, nucleation and dissolution mechanisms for batch cooling crystallization processes is presented. The model based distribution shaping control can be used to design the crystal size distribution of solid products to achieve a desired dissolution profile. By simultaneously optimizing the seed recipe and the supersaturation profile for the crystallization process a tailored dissolution can be achieved. Simulation and experimental studies will be presented to illustrate the potential benefits of the proposed product engineering approach. The population balance model which incorporates both the dissolution and growth mechanism is developed and is solved using a combined quadrature method of moments and method of characteristics approach, which provides a computationally efficient solution of the model, suitable for optimization. The optimization problem is solved to design a fast and a slow dissolution profile, and the operating conditions are evaluated experimentally. The experimental setup includes process analytical technology probes for the monitoring of the crystallization process, including FBRM and ATR-UV/Vis. The approach can have significant potential for application in tailored drug delivery, where the release rate of an active ingredient can be designed by optimizing the dissolution rate. The same approach can have application in case of pesticides for more efficient and environmentally friendly application. Tailoring the particle size distribution of the crystallization product, so that an optimal dissolution rate (heat release rate) is achieved for the case of exothermic reactive processes for which the dissolution is followed by reactions, can improve the safe operation of these systems. Similarly the same strategy can also be applied for reactions, which produce a significant amount of gasses and induce excessive liquid rise, which can lead to the explosion of reactors (two-phase flow can occur in the connection pipes and pressure can build-up).