title: Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.
abstract: Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Margot.Fonteyne@Ugent.be.
authors.forename: Margot
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium; Pharmaceutical Sciences Laboratory, Department of Biosciences, Åbo Akademi University, Turku, Finland.
authors.forename: Henrika
authors.initials: H
authors.lastname: Wickström
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Peeters
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Pharmaceutical Sciences Laboratory, Department of Biosciences, Åbo Akademi University, Turku, Finland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ehlers
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Björn-Hendrik
authors.initials: BH
authors.lastname: Peters
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
authors.affiliation: Pharmaceutical Sciences Laboratory, Department of Biosciences, Åbo Akademi University, Turku, Finland.
authors.forename: Niklas
authors.initials: N
authors.lastname: Sandler
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Naelapää
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: Thomas.Debeer@Ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002626:Chemistry, Pharmaceutical; D006244:Hardness; D007700:Kinetics; D007785:Lactose / Q000737:chemistry* / Q000592:standards; D010316:Particle Size; D016062:Porosity; D011205:Povidone / Q000737:chemistry* / Q000592:standards; D011208:Powders; D025341:Principal Component Analysis; D011786:Quality Control; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength; D013806:Theophylline / Q000737:chemistry* / Q000592:standards
chemical_list: D011208:Powders; D013607:Tablets; D013806:Theophylline; D011205:Povidone; D007785:Lactose
keywords: Continuous pharmaceutical manufacturing; Particle size; Raw material variability; Tableting; Theophylline; Twin screw granulation