title: Simultaneous quantitative analysis of ternary mixtures of D-mannitol polymorphs by FT-Raman spectroscopy and multivariate calibration models.
abstract: D-mannitol is known to exist in five solid-state forms, a hemihydrate, an amorphous form and three polymorphic forms (I(o), II and III), which tend to crystallize concomitantly. Therefore, a fast and simple method for the simultaneous quantification of these polymorphs in powder mixtures was developed on the basis of FT-Raman spectroscopic data, partial least-squares (PLS) regression and artificial neural networks (ANNs). A combination of the first derivative and orthogonal signal correction (OSC) was found to be the optimal data pretreatment that significantly increased the predictive performance of the models. The RMSEPs (root-mean-squared errors of prediction) obtained by PLS for the modifications (mods.) I(o), II and III were 0.44%, 0.34% and 0.36% respectively. The estimated limits of detection are approximately 0.5% (mod. I(o)) and <1% (mods. II and III). The ANNs model yielded slightly higher RMSEP values of 0.51%, 0.39% and 0.41%. In contrast to related previous studies, calibration was performed with carefully prepared ternary mixtures of all polymorphs, which is one of the reasons for the high precision and accuracy of the presented multivariate models.
authors.affiliation: Institute of Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria.
authors.forename: Doris E
authors.initials: DE
authors.lastname: Braun
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Maas
authors.forename: Neslihan
authors.initials: N
authors.lastname: Zencirci
authors.forename: Christoph
authors.initials: C
authors.lastname: Langes
authors.forename: Nora A
authors.initials: NA
authors.lastname: Urbanetz
authors.forename: Ulrich J
authors.initials: UJ
authors.lastname: Griesser
mesh_terms: D002138:Calibration; D003460:Crystallization; D005583:Fourier Analysis; D016018:Least-Squares Analysis; D008353:Mannitol / Q000737:chemistry*; D015999:Multivariate Analysis; D016571:Neural Networks, Computer; D011208:Powders; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D011208:Powders; D008353:Mannitol