(274e) Modelling of Pharmaceutical HME Processes

Josip Matić^*,**, Milica Stanković-Brandl**, Amrit Paudel**,Christophe Herkenne***, Jessica Lovey Martinetti***, Sophie Martel***, Johannes Khinast^*,**

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*Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/III, 8010 Graz, Austria

**Research Centre Pharmaceutical Engineering GmbH, Inffeldgasse 13/III, 8010 Graz, Austria

***Debiopharm Research&Manufacturing S.A., Campus “après-demain”, Rue Levant 146, CP 368, 1920 Martigny, Switzerland

Email for correspondence: khinast@tugraz.at

Introduction

Hot melt extrusion (HME) is a continuous manufacturing process primarily using co-rotating intermeshing twin-screw extruders (TSE). The continuous manufacturing nature of the process allows for a steady product quality and a decrease in production costs. Furthermore, the process has the potential of increasing the bioavailability of poorly soluble drugs by enabling manufacturing of amorphous solid dispersions, making it interesting to the pharmaceutical industry. Although the process has been used in the polymer and rubber industry for years it is still not well enough understood and fairly new in the pharmaceutical industry. The HME setup for new API-polymer system and the technical transfer between different extruder scales (scale-up) are still open question.

Methodology

HME process simulations are done using fully resolved 3D simulations, or by simplified 1D simulation approaches [1-4]. The 1D mechanistic model developer in-house is able to simulate the HME process as a whole, giving information about the filling degree, pressure and temperature distribution, as well as the specific mechanical energy input (SMEC) across the screw configuration[1]. In order to setup the 1D model, the individual screw elements have to be characterized by determining the inherent conveying capacity and the pressure build up capacity[2]. The characterization is done using the mesh-free SPH simulation approach, giving additional insight into the mixing and sheer rate distribution for every screw element, allowing for a comparison between triple- and double-flighted extruder screw element geometries [3].

Results

An HME process on a triple-flighted 16mm extruder, with two different materials, was investigated, providing recommendations for the process setup and scale-up. The validation was done by comparing the experimentally obtained torque; melt temperature and residence time distribution to the in-silico predictions.

Literature

[1] A. Eitzlmayr, G. Koscher, G. Reynolds, Z. Huang, J. Booth, P. Shering, and J. Khinast, “Mechanistic Modeling of Modular Co-Rotating Twin-Screw Extruders,” Int. J. Pharm., vol. 474, no. 1–2, pp. 157–176, 2014.

[2] K. Kohlgrüber, Co-Rotating Twin-Screw Extruders. Munich: Carl Hanser Publishers, 2008.

[3] A. Eitzlmayr, J. Matić, and J. Khinast, “Analysis of Flow and Mixing in Screw Elements of Co-Rotating Twin-Screw Extruders via SPH,” AIChe J.

[4] R. Baumgartner, J. Matić, S. Schrank, S. Laske, J. G. Khinast, and E. Roblegg, “NANEX: Process Design and Optimization,” Internaitonal J. Pharm., vol. 506, pp. 35–45, 2016.