title: Qualitative in situ analysis of multiple solid-state forms using spectroscopy and partial least squares discriminant modeling.
abstract: 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 solid-state forms prior to quantification. The utility of the complementary spectroscopic techniques, NIR and Raman, have been shown.
authors.affiliation: Division of Pharmaceutical Technology, University of Helsinki, Helsinki, Finland.
authors.forename: Karin
authors.initials: K
authors.lastname: Kogermann
authors.forename: Jaakko
authors.initials: J
authors.lastname: Aaltonen
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.forename: Kati
authors.initials: K
authors.lastname: Pöllänen
authors.forename: Peep
authors.initials: P
authors.lastname: Veski
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heinämäki
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003890:Desiccation; D016002:Discriminant Analysis; D016018:Least-Squares Analysis; D008956:Models, Chemical; D044367:Phase Transition; D010894:Piroxicam / Q000737:chemistry*; D033362:Powder Diffraction; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013818:Thermogravimetry; D017186:Titrimetry; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D010894:Piroxicam; D002220:Carbamazepine