title: NIR spectroscopic method for the in-line moisture assessment during drying in a six-segmented fluid bed dryer of a continuous tablet production line: Validation of quantifying abilities and uncertainty assessment.
abstract: This study focuses on the thorough validation of an in-line NIR based moisture quantification method in the six-segmented fluid bed dryer of a continuous from-powder-to-tablet manufacturing line (ConsiGma™ 25, GEA Pharma Systems nv, Wommelgem, Belgium). The moisture assessment ability of an FT-NIR spectrometer (Matrix™-F Duplex, Bruker Optics Ltd, UK) equipped with a fiber-optic Lighthouse Probe™ (LHP, GEA Pharma Systems nv, Wommelgem, Belgium) was investigated. Although NIR spectroscopy is a widely used technique for in-process moisture determination, a minority of NIR spectroscopy methods is thoroughly validated. A moisture quantification PLS model was developed. Twenty calibration experiments were conducted, during which spectra were collected at-line and then regressed versus the corresponding residual moisture values obtained via Karl Fischer measurements. The developed NIR moisture quantification model was then validated by calculating the accuracy profiles on the basis of the analysis results of independent in-line validation experiments. Furthermore, as the aim of the NIR method is to replace the destructive, time-consuming Karl Fischer titration, it was statistically demonstrated that the new NIR method performs at least as good as the Karl Fischer reference method.
authors.affiliation: Laboratory of Pharmaceutical PAT, Ghent University, Harelbekestraat 72, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Department of Chemistry, Universitat Autònoma de Barcelona, UAB, Barcelona, Spain.
authors.forename: Julen
authors.initials: J
authors.lastname: Arruabarrena
authors.affiliation: Drug Analysis, Scientific Institute of Public Health, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: de Beer
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, Analytical Development, Beerse, Belgium.
authors.forename: Mario
authors.initials: M
authors.lastname: Hellings
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, Analytical Development, Beerse, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van Den Kerkhof
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, Analytical Development, Beerse, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Burggraeve
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical PAT, Ghent University, Harelbekestraat 72, Ghent, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002138:Calibration; D003890:Desiccation; D004867:Equipment Design; D005336:Fiber Optic Technology; D011208:Powders; D012015:Reference Standards; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000592:standards; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D013806:Theophylline / Q000737:chemistry*; D013997:Time Factors; D035501:Uncertainty; D014867:Water / Q000032:analysis*
chemical_list: D011208:Powders; D013607:Tablets; D014867:Water; D013806:Theophylline
keywords: Accuracy profiles; Continuous manufacturing; In-line moisture determination; Method validation; PAT