Process Modeling of the Polymorphic Transformation of <scp>l</scp>-Glutamic Acid

Abstract

A simulation model for the solvent-mediated transformation from the metastable α-form to the stable β-form of l-glutamic acid (l-Glu) was developed using the concept of the population balance. The solvent-mediated transformation process is a combination of the dissolution of the α-form and the nucleation and subsequent growth of the β-form. The model parameters for the dissolution of the α-form and the nucleation and growth of the β-form were determined with the aid of experimental data (overall crystal size distribution, polymorphic fraction in solid phase, solute concentration) of 1-L scale batch transformation experiments carried out at several temperatures. The growth rate of the β-form is the rate-limiting step in the transformation. The growth rate constant of the β-form showed an increase with temperature, which is the cause for the experimentally observed transformation rate increase with temperature. The simulation results in detailed information on for example the crystal size distribution change of each form, which is very difficult to measure experimentally. The expected gradual decrease in the peak height of the α-form CSD and the increase in the peak height and the size of the β-form CSD was obtained from the simulation as the transformation proceeded. An adequate combination of experiments and simulations helps to understand and predict crystallization behavior and to optimize polymorphic crystallization processes.