Automated and standardizable approach to quantify crystal nucleation and growth kinetics: Extension to inorganic salts

Determination of crystallization kinetics, specifically for secondary nucleation and crystal growth, often requires significant amounts of time and raw materials. Moreover, resulting kinetic constants are highly dependent on the methodology employed, including factors like scale, mixing, mode of operation (e.g. batch desupersaturation vs continuous crystallization), tools used to measure crystal size, and choice of model including assumptions for estimating supersaturation. These make kinetic parameters difficult to compare across literature, thus hindering advances in our understanding of how solute-solvent interactions and crystallographic properties translate to crystallization kinetic behavior. We hereby present an automated approach to collecting crystallization kinetic data, coupled with standardized equipment and models, for the study of nucleation and growth kinetics for inorganic salts. This approach is an expansion to the already demonstrated methods for weak electrolytes, where data collection is automated in a Technobis Crystalline equipment and in situ imaging data for crystal count and size is processed into kinetic parameters through a population balance model. The main addition in this work is the expansion of that model to account for activity coefficients in strong electrolyte systems, and its demonstration for the antisolvent crystallization of potassium chloride and potassium sulfate from ethanol-water mixtures, quantifying the role of ethanol inhibiting crystallization kinetics for both systems.