title: Blend uniformity evaluation during continuous mixing in a twin screw granulator by in-line NIR using a moving F-test.
abstract: This study focuses on the twin screw granulator of a continuous from-powder-to-tablet production line. Whereas powder dosing into the granulation unit is possible from a container of preblended material, a truly continuous process uses several feeders (each one dosing an individual ingredient) and relies on a continuous blending step prior to granulation. The aim of the current study was to investigate the in-line blending capacity of this twin screw granulator, equipped with conveying elements only. The feasibility of in-line NIR (SentroPAT, Sentronic GmbH, Dresden, Germany) spectroscopy for evaluating the blend uniformity of powders after the granulator was tested. Anhydrous theophylline was used as a tracer molecule and was blended with lactose monohydrate. Theophylline and lactose were both fed from a different feeder into the twin screw granulator barrel. Both homogeneous mixtures and mixing experiments with induced errors were investigated. The in-line spectroscopic analyses showed that the twin screw granulator is a useful tool for in-line blending in different conditions. The blend homogeneity was evaluated by means of a novel statistical method being the moving F-test method in which the variance between two blocks of collected NIR spectra is evaluated. The α- and β-error of the moving F-test are controlled by using the appropriate block size of spectra. The moving F-test method showed to be an appropriate calibration and maintenance free method for blend homogeneity evaluation during continuous mixing.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Fien
authors.initials: F
authors.lastname: De Leersnyder
authors.affiliation: Merck, Oss, The Netherlands.
authors.forename: Rut
authors.initials: R
authors.lastname: Besseling
authors.affiliation: Merck, Oss, The Netherlands.
authors.forename: Ad
authors.initials: A
authors.lastname: Gerich
authors.affiliation: Merck, Oss, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Oostra
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, Ghent, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002138:Calibration; D011208:Powders / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation; D013607:Tablets / Q000138:chemical synthesis / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation
chemical_list: D011208:Powders; D013607:Tablets
keywords: Blend uniformity; Continuous blending; Moving F-test; Near infrared spectroscopy; Process Analytical Technology; α- and β-error control