458336 Scale-up of HME Process from a Trilobed 16mm to a Bilobed 27mm Extruder; SPH Simulations and 1D Mechanistic Modelling
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. Especially the technical transfer between different extruder scales (scale-up) is still an open question.
Simulation of extruders via traditional CFD is prohibitively complex, due to the small gaps, the complex rheology and, especially, due to the free surfaces that occur in the not-fully-filled screw elements. In order to better understand the process conditions and product quality relationships, 1D mechanistic and 3D smoothed particle hydrodynamics (SPH) simulation approaches and the established scale-up theory were used. Standard 3D mesh-based computational fluid dynamics (CFD) models struggle with the complex rotating intermeshing TSE geometry, and lack the ability to investigate partially filed TSE elements. The 1D mechanistic model 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. 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. 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-threaded extruder screw elements.
An HME process on a trilobed 16mm and a bilobed 27mm extruder, with five different materials, was investigated, providing recommendations for the process setup. Additionally, a scale-up scenario was investigated, using the proposed scale-up laws with an in-silico process DoE, with an experimental validation.
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 M. Bierdel, “Computational Fluid Dynamics,” in Co-Rotating Twin-Screw Extruders, K. Kohlgrüber, Ed. Munich: Carl Hanser Publishers, 2008.
 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.
 K. Kohlgrüber, Co-Rotating Twin-Screw Extruders. Munich: Carl Hanser Publishers, 2008.
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