title: Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.
abstract: Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG. Experiments were performed using a 25 mm co-rotating twin screw granulator, being part of the ConsiGma™-25 system (a fully continuous from-powder-to-tablet manufacturing line from GEA Pharma Systems). Besides the screw elements conventionally used for TSG (conveying and kneading elements), alternative designs of screw elements (tooth-mixing-elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-lactose monohydrate formulation granulated with distilled water. Granulation with only conveying elements resulted in wide and multimodal PSD. Using kneading elements, the width of the PSD could be partially narrowed and the liquid distribution was more homogeneous. However, still a significant fraction of oversized agglomerates was obtained. Implementing additional kneading elements or cutters in the final section of the screw configuration was not beneficial. Furthermore, granulation with only TME or SME had limited impact on the width of the PSD. Promising results were obtained by combining kneading elements with SME, as for these configurations the PSD was narrower and shifted to the size fractions suitable for tableting.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Department of Analytical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Burggraeve
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Fonteyne
authors.affiliation: Global Technical Services, Janssen Supply Chain, Janssen Pharmaceutica, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Cappuyns
authors.affiliation: Department of Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Belgium.
authors.forename: U
authors.initials: U
authors.lastname: Delaet
authors.affiliation: Department of Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Van Assche
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium. Electronic address: Chris.Vervaet@ugent.be.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D007785:Lactose
keywords: Continuous processing; Particle size distribution; Process understanding; Screw configuration; Twin screw granulation