In‐line monitoring of reactive crystallization process based on ATR–FTIR and Raman spectroscopy

The paper studies the utilization of attenuated total reflectance–Fourier transformed infrared (ATR–FTIR) and Raman spectroscopy to investigate isothermal semi‐batch precipitation of a model compound, L‐glutamic acid. ATR–FTIR spectroscopy was mainly used for in‐line monitoring of the solution phase and Raman spectroscopy for analysis of the solid phase. L‐glutamic acid has two reported polymorphs: a metastable α form and a stable β form. The β form can be obtained at relatively high supersaturation levels at 25°C. The synthesis consists of a sodium glutamate reaction with sulfuric acid yielding L‐glutamic acid crystals and sodium sulfate as a side‐product solute. The spectral data were utilized to interpret the crystallization process using multivariate methods. A thermodynamic model taking into account the non‐ideal character of the studied compound system and dissociation of different compounds is introduced. The resolution of ATR–FTIR is not sufficient to determine directly the L‐glutamic acid concentration in the solution. Therefore, special efforts were made to determine the instantaneous concentration of dissolved glutamic acid based on the mass balance and ATR–FTIR spectra. Calibration concentrations were based on thermodynamic data. Multivariate methods were applied in monitoring the precipitation process and to predict indirectly the concentration of the chemical compounds. In this study, the spectra from ATR–FTIR were utilized to estimate and predict the concentrations from thermodynamic modeling. It was also investigated if the Raman spectra could be used for this purpose. Copyright © 2008 John Wiley & Sons, Ltd.