title: Sensitive NIRS measurement of increased moisture in stored hygroscopic freeze dried product.
abstract: The purpose of this study was to build a best possible NIR prediction model for monitoring of water content in a freeze-dried drug product. The best pre-treatments of the NIR spectra were found to be: transforming from reflection to absorption, baseline correction in the 1845-2165 nm area and a maximum normalisation in the same area. These pre-treatments resulted in a model with the following attributes: SEP of 0.08% (w/w) and one PLS factor, the latter indicating a robust model. The limit of quantification was calculated to 0.24% (w/w). During the stability study an increase in water content in the freeze-dried drug product was revealed, which were found to depend on storage time and temperature. It is believed that the water is derived from the stoppers. The highest increase was found for storage at 40 degrees C, and was estimated to be 0.04% points a month by weight, from an initial value of about 0.25% (w/w).
authors.affiliation: Chemical Development, Oslo Plant, Nycomed Imaging AS, P.O. Box 4220, Nydalen, N-0401, Oslo, Norway. anders.stokvold@no.nycomed-amersham.com
authors.forename: Anders
authors.initials: A
authors.lastname: Stokvold
authors.forename: Knut
authors.initials: K
authors.lastname: Dyrstad
authors.forename: Fred Olav
authors.initials: FO
authors.lastname: Libnau
mesh_terms: D002138:Calibration; D004356:Drug Storage; D005612:Freeze Drying; D008962:Models, Theoretical; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared; D013696:Temperature; D014867:Water / Q000032:analysis*
chemical_list: D014867:Water