Qualitative in situ analysis of multiple solid-state forms using spectroscopy and partial least squares discriminant modeling

Karin Kogermann, Jaakko Aaltonen, Clare Strachan, Kati Pöllänen, Peep Veski, Jyrki Heinämäki, Jouko Yliruusi, Jukka Rantanen

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    This study used in situ spectroscopy to reveal the multiple solid-state forms that appear during isothermal dehydration. Hydrate forms of piroxicam and carbamazepine (CBZ) were investigated on hot-stage at different temperatures using near-infrared (NIR) and Raman spectroscopy combined with multivariate modeling. Variable temperature X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and Karl Fisher titrimetry were used as reference methods. Partial least squares discriminant analysis (PLS-DA) was performed to qualitatively evaluate the phase transition. It was shown that the constructed PLS-DA models, where spectral differences were directly correlated to solid-state modifications, enabled differentiation between the multiple forms. Qualitative analysis revealed that during dehydration, hydrates, such as CBZ dihydrate, may go through several solid-state forms, which must be considered in quantitative model construction. This study demonstrates that in situ analysis can be used to monitor the dehydration and reveal associated solidstate forms prior to quantification. The utility of the complementary spectroscopic techniques, NIR and Raman, have been shown. (c) 2007 Wiley-Liss, Inc.
    Original languageEnglish
    JournalJournal of Pharmaceutical Sciences
    Issue number7
    Pages (from-to)1802-1820
    Number of pages19
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

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