title: IR spectroscopy together with multivariate data analysis as a process analytical tool for in-line monitoring of crystallization process and solid-state analysis of crystalline product.
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.
authors.affiliation: Lappeenranta University of Technology, Department of Chemical Technology, Laboratory of Separation Technologies, P.O. Box 20, 53851 Lappeenranta, Finland. Kati.Pollanen@lut.fi
authors.forename: Kati
authors.initials: K
authors.lastname: Pöllänen
authors.forename: Antti
authors.initials: A
authors.lastname: Häkkinen
authors.forename: Satu-Pia
authors.initials: SP
authors.lastname: Reinikainen
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Milja
authors.initials: M
authors.lastname: Karjalainen
authors.forename: Marjatta
authors.initials: M
authors.lastname: Louhi-Kultanen
authors.forename: Lars
authors.initials: L
authors.lastname: Nyström
mesh_terms: D000465:Algorithms; D003460:Crystallization / Q000379:methods; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013055:Spectrophotometry, Infrared / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations