Monitoring of Antisolvent Addition Crystallization with Raman Spectroscopy

Fiber optic 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 DSC. Raman spectroscopy was used to monitor dehydration during storage of the product crystals. The current study demonstrates the advantages of using Raman spectroscopy to monitor the solution phase during crystallization and simultaneously monitoring the solid-state form.