Rapid, low-cost exploration of nucleation rates in l-glutamic acid crystallization in pure media and the presence of polymers through novel parallel experimentation

Abstract

Crystal nucleation is crucial in various fields of science and technology, ranging from materials synthesis to pharmaceutical production. Our research aims to determine the nucleation rates from parallel induction time measurement experiments followed by low-cost external bulk video imaging. Stirred conditions are applied, making our results industry-relevant where the crystallizers are also mixed. The L-Glutamic Acid-water system (L-GA/water) is used as a surrogate. The study is conducted through a series of parallel, small-scale stirred experiments that explore the effects of supersaturation, temperature, and polymer additives on nucleation rates. The methodology involves careful data collection through controlled experimental setup and analysis of induction time distributions that the stochastic nature of nucleation explains the induction time distribution. The discussion section interprets the findings within the context of the research question, highlighting the implications of varying temperature and supersaturation levels as two experimental parameters and polymers on crystal nucleation rates. The specific parameters of supersaturation and temperature dependencies are in the range of those reported in the literature, which validated the developed rapid nucleation rate measurement platform. Stepping outside of these established measurements, analyzing the influence of polymers with high potential in controlling particle size, shape, and polymorphism was touched as well. As an unexpected result, the nucleation rates appeared to depend not only on the chemical structure and amount of the polymer but also on the polymer solution preparation method. The remarkable influence of polymers on nucleation rates was shown that cannot be explained with the solubility altering effect of the polymers alone.