Solubility and Metastable Zone Width

Solubility and Metastable Zone Width (MSZW) curves are critical parameters for the definition of the operational and optimal design space for a crystallization process. They supply the upper and lower limits of operation as well as provide a definition of the maximum theoretical yield for a given system. Even though there are many solutions for small-scale screening which are useful for solvent selection, one must be careful in applying the information collected from small-scale screening experiments to process scale-up.

The MSZW is especially sensitive to scale-up effects resulting from changes in the mixing apparatus and vessel configuration. Mapping of the MSZW should ideally be confirmed upon scale-up to adjust for the effects of temperature and concentration gradients that are inevitable at larger scale. An initial characterization at the laboratory scale typically provides reliable guidance for scale up. The resulting models can be easily tested and fine-tuned using appropriate process analytical tools during scale-up or technology transfer to ensure consistent results.

There is additional value in using advanced measurements such as FBRM and/or ReactIR for confirmation of the MSZW during scale-up. These multivariate measurements provide additional capability that can be used to characterize crystallization kinetics (with FBRM) or supersaturation (with ReactIR) – providing a deeper understanding for improved optimization , scale-up and control.