Content overview
Crystallization is a critical process in industries such as pharmaceuticals, agrochemicals, and cosmetics, but controlling crystal size and quality remains challenging due to competing phenomena like nucleation, growth, and agglomeration. Population Balance Modeling (PBM) helps predict crystal size distributions by calculating nucleation and growth kinetics, enabling better process optimization.
The Crystalline platform introduces a new PBM feature that allows researchers to determine nucleation (Kb) and growth (Kg) constants using only a few milliliters of sample and a small amount of material. With eight independently controlled reactors, high-resolution imaging, and optional Raman spectroscopy, the system provides real-time monitoring of crystal size, shape, and polymorphism during crystallization experiments.
Case studies on paracetamol and potassium sulfate demonstrate how solvent composition influences crystallization behavior. For paracetamol, ethanol/water mixtures produced approximately ten times higher nucleation and growth rates than pure ethanol, while for potassium sulfate, adding ethanol reduced crystal growth without affecting nucleation, allowing particle size to be tailored through solvent selection.
Overall, the Crystalline PBM approach enables scientists to screen solvents, understand crystallization kinetics, and optimize process conditions much earlier in development than traditional methods. This reduces material and time requirements while supporting better process decisions and more efficient crystallization development.
References
1. Automated and Material-Sparing Workflow for the Measurement of Crystal
Nucleation and Growth Kinetics; Ryan J. Arruda, Paul A.J. Cally, Anthony Wylie,
Nisha Shah, Ibrahim Joel, Zachary A. Leff, Alexander Clark, Griffin Fountain,
Layane Neves, Joseph Kratz, Alpana A. Thorat, Ivan Marziano, Peter R. Rose,
Kevin P. Girard, and Gerard Capellades; Crystal Growth & Design 2023 23 (5),
3845-3861; DOI: 10.1021/acs.cgd.3c00252
