Process Analytical Techniques Based on In-Line Vibrational Spectroscopy and their Industrial Applications

Process analytical techniques (PAT) involve the monitoring and control of physical and chemical processes as well as the identification of important process parameters in order to obtain the products with desired properties. PAT have been applied in various industrial process phases to ensure better process understanding, quality by optimal design and determination of process disturbances in time. In-line vibrational spectroscopic techniques are one of the major process analytical techniques used today. The most frequently used in-line vibrational spectroscopic techniques are near infrared spectroscopy (NIR), attenuated total reflectance middle infrared spectroscopy (ATR-MIR) and Raman spectroscopy (Table 1, Figs. 1 and 2). They provide in situ real-time monitoring of the production processes by using different types of in-line probes (Figs. 3–5) which reduce exposure to hazardous materials and contamination, sample degradation or equilibrium perturbations in the reaction system. Due to the aforementioned advantages, in-line vibrational spectroscopic techniques have been successfully applied for different industrial pur- poses. The analysis of characteristic vibrational bands in in-line infrared and Raman spectra enable the monitoring of different processes such as crystallization, dissolution, polimorphic transitions and chemical reactions (Scheme 1, Figs. 6 and 7). The obtained data are, due to their complexity, very often further processed by multivariate data analysis methods (Fig. 9), such as principal components analysis (PCA) and partial least squares (PLS). The basic principles of PCA and PLS are shown in Fig. 8. A number of different in-line vibrational spectroscopic techniques as well as multivariate data analysis methods have been developed recently, but in this article only the most important and most frequently used techniques are described. KUI – 7/2013 Received April 10, 2012 Accepted July 18, 2012