Aaltonen Jaakko, Strachan Clare J, Pöllänen Kati, Yliruusi Jouko, Rantanen Jukka
Division of Pharmaceutical Technology, P.O. Box 56, 00014 University of Helsinki, Finland.
J Pharm Biomed Anal. 2007 Jun 28;44(2):477-83. doi: 10.1016/j.jpba.2007.02.009. Epub 2007 Feb 13.
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.
对一种模型化合物（呋喃妥因）进行了多晶型筛选。呋喃妥因从具有不同工艺参数的丙酮 - 水混合物中结晶。在多晶型筛选中结晶出了两种无水物形式（α和β）和一种一水合物形式（II）。使用三种互补的光谱技术对固体形式进行了分析：近红外（NIR）光谱、拉曼光谱和太赫兹脉冲光谱（TPS），并且通过X射线粉末衍射（XRPD）验证了固相分析的结果。将近红外光谱和拉曼光谱联用，以实现一种快速且全面的固相分析方法。用多元方法主成分分析（PCA）分析了联用的近红外/拉曼光谱数据。由于这些方法具有互补特性，发现这种组合在筛选固体形式方面是有效的。近红外光谱在区分无水物和水合物形式以及分子间特征方面很强大；而拉曼光谱对分子主链中的分子内变化敏感。
