Raman, UV, NIR, and Mid-IR Spectroscopy with Focused Beam Reflectance Measurement in Monitoring Polymorphic Transformations

Raman, UV, NIR, and IR spectroscopy are commonly used techniques to monitor solute concentration and solid composition during crystallization processes of polymorphic compounds. Since a comprehensive study and comparison of the ability of these techniques to detect polymorphic transformation in the same system has not been performed yet, this work aimed at developing a complete quantitative calibration model that describes the process in terms of solute concentration and solid composition for each technique. A comparison between the different process analytical technology tools was conducted using various physical and mathematical approaches. Chemometrics techniques, multivariate and univariate approaches, and different regression techniques were tested and an integrated calibration model is proposed. The most common techniques for in situ monitoring of polymorphic transformation are compared and evaluated. The proposed integrated approach which combines signals from two process analytical technology tools to include solid concentration in the calibration model of polymorphic composition can provide accurate calibration faster and with less material required.