Fiber optic Raman spectroscopy was used for in situ monitoring of antisolvent addition crystallization of progesterone. Raman spectral features of the solute and the antisolvent were subjected to principal components analysis (PCA) to attempt to obtain information that 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 antisolvent. Furthermore, PCA was capable of detecting subtle changes in the spectral data (as the addition of antisolvent 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.
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