title: Hyphenated spectroscopy as a polymorph screening tool.
abstract: Polymorph screening of a model compound (nitrofurantoin) was performed. Nitrofurantoin was crystallized from acetone-water mixtures with varying process parameters. Two anhydrate forms (alpha and beta) and one monohydrate form (II) were crystallized in the polymorph screen. The solid forms were analyzed with three complementary spectroscopic techniques: near-infrared (NIR) spectroscopy, Raman spectroscopy and terahertz pulsed spectroscopy (TPS), and the results of the solid phase analysis were verified with X-ray powder diffraction (XRPD). NIR and Raman spectroscopy were coupled to achieve a rapid and comprehensive method of solid phase analysis. The hyphenated NIR/Raman spectroscopic data were analyzed with a multivariate method, principal component analysis (PCA). The combination was found effective in screening solid forms due to the complementary characteristics of the methods. NIR spectroscopy is powerful in differentiating between anhydrate and hydrate forms and intermolecular features, whereas Raman spectroscopy is sensitive to intramolecular alterations in the molecular backbone.
authors: Division of Pharmaceutical Technology, P.O. Box 56, 00014 University of Helsinki, Finland. jaakko.aaltonen@helsinki.fi
authors: Jaakko
authors: J
authors: Aaltonen
authors: Clare J
authors: CJ
authors: Strachan
authors: Kati
authors: K
authors: Pöllänen
authors: Jouko
authors: J
authors: Yliruusi
authors: Jukka
authors: J
authors: Rantanen
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D007536:Isomerism; D015999:Multivariate Analysis; D009582:Nitrofurantoin / Q000737:chemistry / Q000302:isolation & purification; D025341:Principal Component Analysis; D019265:Spectroscopy, Near-Infrared; D013057:Spectrum Analysis / Q000379:methods*; D013059:Spectrum Analysis, Raman
chemical_list: D009582:Nitrofurantoin