Nucleation and growth kinetics estimation for l-phenylalanine hydrate and anhydrate crystallization

A process model for the crystallization of l-phenylalanine crystals from mixed propanol-water solution, an enantiotropic system, is developed with nucleation and growth kinetics estimated for the anhydrate and monohydrate forms using in situ ATR-FTIR spectroscopy and laser backscattering. A challenging aspect of estimating kinetics for this system is the formation of large numbers of small crystals under certain conditions, which result in biases in the data collected from in situ ATR-FTIR and FBRM probes. Batch experiments were designed to follow particular trajectories in the phase diagram so that some kinetic phenomena are suppressed in some runs, which enabled the estimation of sets of kinetic parameters in stages, reducing the number of parameters to be estimated simultaneously. The model was validated by comparison of model predictions and experiments for the product crystals and metastable limits obtained from independent characterization and experiments. This combination of experimental design and process modeling may be emulated to facilitate process modeling and development for crystallizations involving multiple crystal structures. © The Royal Society of Chemistry 2011.