title: Towards a robust water content determination of freeze-dried samples by near-infrared spectroscopy.
abstract: The possibility for determination of the water content in pharmaceutical samples by near-infrared (NIR) spectroscopy has been more widely investigated in the past few years. However, many studies claim that changes in sample composition will require the establishment of a new method. The aim of this study was several fold: firstly to investigate validation aspects of water content determination in samples with varying composition and furthermore to see if a model based solely on freeze-dried mannitol-sucrose mixtures can be established that will be able to predict water contents for samples containing proteins, excipients or having a lower density of freeze-dried solids. Samples were measured by NIR, standard normal variate (SNV) corrected and the obtained spectra were compared with the results from a conventional Karl-Fischer titration by means of multivariate analysis, namely principal component analysis (PCA) and partial least square regression (PLS). For the overall sample set, a highly linear correlation between the NIR and the Karl-Fischer method with a slope of 1.00, an R(2) value of 0.98 and a root mean square error of cross-validation (RMSECV) of 0.15% were found. In a second step samples solely consisting of mannitol and sucrose mixtures were used to build a calibration set, which resulted in a RMSECV of 0.16%. The prediction of the remaining samples, which included protein or excipient containing samples, as well as lower density samples, resulted in a root mean square error of prediction (RMSEP) of 0.19%. Thus the present study demonstrated, that a general model for the determination of the water content by NIR could be established, within the limits investigated.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. hgr@farma.ku.dk
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.forename: Delphine
authors.initials: D
authors.lastname: Gildemyn
authors.forename: Erik
authors.initials: E
authors.lastname: Skibsted
authors.forename: James M
authors.initials: JM
authors.lastname: Flink
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D005612:Freeze Drying; D016018:Least-Squares Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry; D025341:Principal Component Analysis; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014867:Water / Q000032:analysis*
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water