Thermodynamic model for predicting progress of equilibrium limited reactive crystallizations

Reactive crystallizations enable process streamlining by combining reaction and crystallization together in one processing step. In many cases, reactive crystallizations could be equilibrium limited due to the inherent nature of the participating chemical species. There is a need to understand the rate of generation of supersaturation in such crystallizations to develop purification and particle engineering strategies. The delivery burden on reactive crystallizations is immense if they are a part of the terminal Active Pharmaceutical Ingredient (API) synthesis and isolation. In this article, we discuss reactive crystallization for an API and develop a thermodynamic model to predict the progress of equilibrium limited reactive crystallizations. We discuss in detail the formulation of the model and demonstrate that the model can successfully be applied to the crude reaction mixture. The framework discussed in this work can be implemented in trivial spreadsheets and could be readily applied to model various equilibrium limited reactive crystallizations.