title: Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation.
abstract: The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin-screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation design approach and formulation optimization. A total of 9 preferred fillers and 9 preferred binders were selected for this study. The selected fillers and binders were extensively characterized regarding their physico-chemical and solid state properties using 21 material characterization techniques. Subsequently, principal component analysis (PCA) was performed on the data sets of filler and binder characteristics in order to reduce the variety of single characteristics to a limited number of overarching properties. Four principal components (PC) explained 98.4% of the overall variability in the fillers data set, while three principal components explained 93.4% of the overall variability in the data set of binders. Both PCA models allowed in-depth evaluation of similarities and differences in the excipient properties.
authors.affiliation: Small Molecules Technical Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Willecke
authors.affiliation: Small Molecules Technical Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Szepes
authors.affiliation: Small Molecules Technical Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Wunderlich
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium. Electronic address: Thomas.DeBeer@Ugent.be.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D008970:Molecular Weight; D010316:Particle Size; D025341:Principal Component Analysis; D012995:Solubility; D013500:Surface Tension; D014783:Viscosity; D014867:Water / Q000032:analysis; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D014867:Water
keywords: Continuous twin-screw wet granulation; Excipient characterization; Multivariate data analysis; Principal component analysis (PCA); Quality by Design (QbD)