Model-based approach to the design of pharmaceutical roller-compaction processes

Peter Toson; Diogo G Lopes; Raphael Paus; Ashish Kumar; Jeroen Geens; Sandy Stibale; Julian Quodbach; Peter Kleinebudde; Wen-Kai Hsiao; Johannes Khinast

doi:10.1016/j.ijpx.2019.100005

Model-based approach to the design of pharmaceutical roller-compaction processes

Int J Pharm X. 2019 Jan 26:1:100005. doi: 10.1016/j.ijpx.2019.100005. eCollection 2019 Dec.

Authors

Affiliations

¹ Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
² Discovery, Product Development and Supply, Pharmaceutical Research and Development, Division of Janssen Pharmaceutica, Johnson & Johnson, Turnhoutseweg 30, B-2340 Beerse, Belgium.
³ Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
⁴ Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.

Abstract

This work presents a new model based approach to process design and scale-up within the same equipment of a roller compaction process. The prediction of the operating space is not performed fully in-silico, but uses low-throughput experiments as input. This low-throughput data is utilized in an iterative calibration routine to describe the behavior of the powder in the roller compactor and improves the predictive quality of the mechanistic models at low and high-throughput. The model has been validated with an experimental design of experiments of two ibuprofen formulations. The predicted sweet spots in the operating space are in good agreement with the experimental results.

Keywords: Design space prediction; Roller compaction; Solid fraction; Throughput.