(343e) Application of Combined Experimental and Modeling Approach to Understand pH Driven Reactive Crystallization

Application of Combined Experimental and Modeling Approach to Understand pH driven Reactive Crystallization

Authors: Shankar Vaidyaraman, Edward Conder, Gregory Brown, Angela Stack, Michael Phillips, Shekhar Viswanath, Eric Moher

Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285

This talk will discuss a combined experimental and modeling approach to understand pH driven reactive crystallization. A mechanistic approach was taken by using experiments to determine the fundamental parameters of the system (pKa, solubility product, pseudo-growth constant). A “fit for use” mechanistic model accounting for the different reaction equilibria in solution was used to link the fundamental parameters to process parameters (addition type, pH during crystallization, time duration of crystallization etc.). The model was used to help plan experiments to understand the impact of flow upsets on pH excursion during crystallization. The model was also used to generate a response surface of pH vs other process parameters to provide guidance to pH controller design.