In situ process monitoring using Raman spectroscopy

The ability to monitor processes in situ provides many advantages over more conventional off-line analyses. Fundamentally, in situ monitoring can aid in the development of more in depth process understandings and allow for greater process control. On a more practical level, in situ monitoring can reduce sample analysis time and allow for increased analysis automation. These advantages ultimately translate to a more robust and reproducible process. Current studies demonstrate the superior capability Raman spectroscopy provides for in situ monitoring of various processes.;Raman spectroscopy was used for in situ monitoring of antisolvent addition crystallization of cortisone acetate. Raman spectral features of the solvent, the antisolvent, and the solute were monitored to measure the relative concentration of the components. Different rates of antisolvent addition were monitored and the resulting solid-state form was characterized using Raman spectroscopy and differential scanning calorimetry (DSC). Raman spectroscopy was used to monitor dehydration during storage of the product crystals. This work demonstrates the advantages of using Raman spectroscopy to monitor the solution phase during crystallization and simultaneously monitoring the solid-state form.;In addition, Raman spectroscopy was used for in situ monitoring of anti-solvent addition crystallization of progesterone. Raman spectral features of the solute and the anti-solvent were subjected to principal components analysis (PCA) in order to attempt to obtain information which is not readily apparent from the raw spectral data. For the system utilized, PCA was able to distinguish spectral features from the solute in solution, the solute crystals and the anti-solvent. Furthermore, PCA was capable of detecting subtle changes in the spectral data (as the addition of anti-solvent progressed) that could be used as a warning for the onset of crystallization. The current study demonstrates the advantages that can be gained by combining PCA with Raman spectroscopy for monitoring crystallizations in situ .;A novel dispersive Raman spectroscopic procedure for the in situ monitoring of fatty acid cis to trans isomerization in edible oils is also described. The rapid determination of trans isomer content in edible oils is of great importance in the characterization of fats and oils in the food industry. Raman spectral changes observed during the high temperature heating of oil were correlated with cis and trans isomer concentration determined by gas chromatography (GC). The short acquisition times, low laser power and ease of application of dispersive Raman spectroscopy using an NIR excitation source combined with the correlation derived from the GC data provided the capability of monitoring the isomerization in situ. The method developed here has potential applications for increased process control of edible oil hydrogenation, deodorization and quality control among other widely used processing steps. The in situ monitoring capability provided by dispersive Raman spectroscopy offers considerable advantages over the conventional off-line FT-Raman spectroscopy analysis.