Rapid Assessment of Crystal Nucleation and Growth Kinetics: Comparison of Seeded and Unseeded Experiments

In this work, we outlined an experimental workflow enabling the rapid assessment of primary and secondary nucleation and crystal growth kinetics. We used small-scale experiments in agitated vials with in situ imaging for crystal counting and sizing to quantify nucleation and growth kinetics of α-glycine in aqueous solutions as a function of supersaturation at isothermal conditions. Seeded experiments were required to assess crystallization kinetics when primary nucleation is too slow, especially at lower supersaturations often encountered in continuous crystallization processes. At higher supersaturations, we compared results from seeded and unseeded experiments and carefully analyzed interdependencies of primary and secondary nucleation and growth kinetics. This approach allows for the rapid estimation of absolute values of primary and secondary nucleation and growth rates without relying on any specific assumptions about functional forms of corresponding rate expressions used for estimation approaches based on fitting population balance models. Quantitative relationships between nucleation and growth rates at given conditions provide useful insights into crystallization behavior and can be explored to rationally manipulate crystallization conditions for achieving desirable outcomes in batch or continuous crystallization processes.