title: Analysis of large-scale tablet coating: Modeling, simulation and experiments.
abstract: This work concerns a tablet coating process in an industrial-scale drum coater. We set up a full-scale Design of Simulation Experiment (DoSE) using the Discrete Element Method (DEM) to investigate the influence of various process parameters (the spray rate, the number of nozzles, the rotation rate and the drum load) on the coefficient of inter-tablet coating variation (cv,inter). The coater was filled with up to 290kg of material, which is equivalent to 1,028,369 tablets. To mimic the tablet shape, the glued sphere approach was followed, and each modeled tablet consisted of eight spheres. We simulated the process via the eXtended Particle System (XPS), proving that it is possible to accurately simulate the tablet coating process on the industrial scale. The process time required to reach a uniform tablet coating was extrapolated based on the simulated data and was in good agreement with experimental results. The results are provided at various levels of details, from thorough investigation of the influence that the process parameters have on the cv,inter and the amount of tablets that visit the spray zone during the simulated 90s to the velocity in the spray zone and the spray and bed cycle time. It was found that increasing the number of nozzles and decreasing the spray rate had the highest influence on the cv,inter. Although increasing the drum load and the rotation rate increased the tablet velocity, it did not have a relevant influence on the cv,inter and the process time.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Boehling
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Toschkoff
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Knop
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Kleinebudde
authors.affiliation: Global Chemical and Pharmaceutical Development, Bayer Pharma AG Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Just
authors.affiliation: Global Chemical and Pharmaceutical Development, Bayer Pharma AG Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Funke
authors.affiliation: L.B. Bohle Maschinen+Verfahren GmbH, Ennigerloh, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Rehbaum
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria.
authors.forename: J G
authors.initials: JG
authors.lastname: Khinast
mesh_terms: D000465:Algorithms; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D004345:Drug Industry / Q000295:instrumentation* / Q000379:methods*; D008962:Models, Theoretical; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*
chemical_list: D013607:Tablets
keywords: DEM; GPU simulation; Industrial scale simulation; Tablet coating