Development and Validation of a Raman Spectroscopy Concentration Calibration Model to Enhance Crystallization Kinetic Model-Based Control: A Case Study of DL-methionine

Crystallization, as the final step of production, has a significant impact on the crystal properties, including particle size distribution (PSD), crystal habit, and crystal form. By applying the process analysis technique (PAT), the crystallization process can be monitored and the crystallization parameters can be regulated to obtain higher quality crystals. This work demonstrates the development and validation of a Raman spectroscopy concentration calibration model for monitoring the DL-methionine solute concentration. The results show that the Raman spectroscopy concentration calibration model can obtain an accurate concentration change of the crystallization process, and the relative standard deviations of the repeatability and intermediate precision were less than 5%. Then, concentration variations of the crystallization process obtained by Raman spectroscopy were used to determine the exact crystallization kinetic parameters of beta-DL-methionine by solving the population balance equation (PBE). After that, the PSD under other conditions was simulated by inputting kinetic data into the PBE. Moreover, the impact of the crystallization operation parameters on the product particle size was investigated. It was observed that either increasing the temperature or supersaturation of the crystallization process could increase the particle size of the crystallized product.