Applied chemometrics in crystallization monitoring

Crystallization is an industrially important unit operation due to its ability to provide high purity separations, which explains its predominant use in the pharmaceutical industry. Characterization of the different fundamental mechanisms during crystallization processes, i.e. nucleation, growth and polymorphic transformations, is crucial for control and ability to predict crystal properties.

In-situ process monitoring tools, such as Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy, Focused Beam Reflectance Measurements (FBRM) and Raman spectroscopy have gained increasing importance for the design of crystallization processes. In recent years it was demonstrated for various applications, how these process analytical technologies (PATs) can be employed for an enhanced process understanding and rational process design. By using ATR-FTIR spectroscopy supersaturation can be monitored, FBRM is used to reveal information about PSD (chord length distribution as measured in FBRM) and Raman spectroscopy can be employed to study polymorph transformations.

Although spectroscopic techniques are often applied for crystallization process monitoring, the analysis of spectroscopic measurement data has often proven to be challenging. The application of chemometric methods for the spectroscopic data analysis, which is established as a standard technique in analytical chemistry, has received increasing attention in the field of crystallization monitoring. The objective of this work is to study in detail, how the analysis of spectroscopic and other kind of monitoring data can be improved by means of chemometric methods for the application in crystallization processes.

Further reading:
[1] Brereton, R. G. The Analyst, 2000, 125, 2125-2154
[2] Lavine, B.; Workman, J. Anal. Chem. 2006, 78, 4137-4145
[3] Cornel, J.; Lindenberg, C.; Mazzotti, M., Ind. Eng. Chem. Res 2008, 47, 4870-4882
[4] Cornel, J.; Lindenberg, C.; Mazzotti, M., Cryst. Growth Des. 2009, in press