title: Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation.
abstract: Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution within each module where different granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients.
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium; Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: ashish.kumar@ugent.be.
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: jurgen.vercruysse@ugent.be.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercruysse
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: valerie.vanhoorne@ugent.be.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanhoorne
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre, Kuopio, Finland. Electronic address: maunu.toiviainen@vtt.fi.
authors.forename: Maunu
authors.initials: M
authors.lastname: Toiviainen
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre, Kuopio, Finland. Electronic address: pierre-emmanuel.panouillot@vtt.fi.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Panouillot
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre, Kuopio, Finland. Electronic address: mikko.juuti@vtt.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Juuti
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: chris.vervaet@ugent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: jeanpaul.remon@ugent.be.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: CAPEC-PROCESS, Department of Chemical and Biochemical Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. Electronic address: kvg@kt.dtu.dk.
authors.forename: Krist V
authors.initials: KV
authors.lastname: Gernaey
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: thomas.debeer@ugent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium. Electronic address: ingmar.nopens@ugent.be.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Nopens
mesh_terms: D004339:Drug Compounding / Q000295:instrumentation*; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008962:Models, Theoretical
chemical_list: D005079:Excipients; D007785:Lactose
keywords: Axial mixing; Flow modelling; Residence time distribution; Stagnant zone; Wet granulation