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Updated: Aug 17, 2026

Crystallization and In Situ Room Temperature Data Collection Using the Crystallization Facility at Harwell and Beamline VMXi, Diamond Light Source
Published on: March 8, 2024
IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of
Kati Pöllänen1, Antti Häkkinen, Satu-Pia Reinikainen
1Lappeenranta University of Technology, Department of Chemical Technology, Laboratory of Separation Technologies, P.O. Box 20, 53851 Lappeenranta, Finland. Kati.Pollanen@lut.fi
Abstract:
Crystalline product should exist in optimal polymorphic form. Robust and reliable method for polymorph characterization is of great importance. In this work, infra red (IR) spectroscopy is applied for monitoring of crystallization process in situ. The results show that attenuated total reflection Fourier transform infra red (ATR-FTIR) spectroscopy provides valuable information on process, which can be utilized for more controlled crystallization processes. Diffuse reflectance Fourier transform infra red (DRIFT-IR) is applied for polymorphic characterization of crystalline product using X-ray powder diffraction (XRPD) as a reference technique. In order to fully utilize DRIFT, the application of multivariate techniques are needed, e.g., multivariate statistical process control (MSPC), principal component analysis (PCA) and partial least squares (PLS). The results demonstrate that multivariate techniques provide the powerful tool for rapid evaluation of spectral data and also enable more reliable quantification of polymorphic composition of samples being mixtures of two or more polymorphs. This opens new perspectives for understanding crystallization processes and increases the level of safety within the manufacture of pharmaceutics.
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