(83b) Implementation of a High-Resolution Population Balance Solver to Model Pharmaceutical Crystallizations

Implementing a successful Quality-by-Design (QbD) strategy involves the construction and evaluation of adequate models describing the quantitative relationships between process parameters and intermediate/API quality.  In the crystallization of the API, the quality of the product is dictated not only by the chemical purity of the product but also by its physical properties.  Therefore, high fidelity models that accurately describe the API properties such as surface area and particle size distribution as a function of the crystallization parameters in the final isolation are indispensable resources of any QbD strategy.  Population balance models (PBM’s) have been shown to be powerful tools in the description of crystallization processes.  This work implements a high resolution PBM solver to model the crystallization of an API.  The data used for parameter regression were obtained from crystallizations incorporating a constant supersaturation control strategy that allows the crystallizations to operate under predominantly growth or secondary nucleation regimes.  The model was subsequently used as a guide for a design space that ensured control of the desired particle size distribution of the API.