(656c) In silico Process Design and Scale-up for an Amorphous Solid Dispersion Manufactured By Hot Melt Extrusion | AIChE

(656c) In silico Process Design and Scale-up for an Amorphous Solid Dispersion Manufactured By Hot Melt Extrusion


Meyer, J., UCB
Ambardekar, R., Pfizer WWRD
McAllister, M., Pfizer WWRD
Pinto, M., Pfizer WWRD
Doshi, P., Worldwide Research and Development, Pfizer Inc.
Khinast, J. G., Graz University of Technology
Jajcevic, D., Research Center Pharmaceutical Engineering Gmbh
Email for correspondence: josip.matic@rcpe.at, EwaldJonathan.Meyer@pfizer.com
Hot melt extrusion (HME) is a continuous manufacturing process increasingly used as an environmentally sustainable technique to produce amorphous solid dispersions (ASDs) of poorly water soluble active pharmaceutical ingredients (APIs). The extruders used for the processing are module co-rotating intermeshing twin screw extruders. A careful selection of the screw configuration and process parameters is required for achieving a stable ASD. Considering potential process setup permutations and it being a continuous manufacturing technology, HME requires high amounts of API than typically available in the early development stages. Additionally, significant experimental iterations are required to generate substantial process understanding for establishing controls that would apply from development to commercial scales. To address these challenges, our groups have worked on the development of in silico and experimental tools for simpler process development and scale-up.
To this date, most of the HME process development and scale-up activities are performed experimentally and empirically. To enhance sustainability and the speed of rational, science-based process development, the objective of this work was to create supportive in silico tools [1]–[9]. The fundamental idea behind HME process modeling is the breakdown and the detailed analysis of the key process aspects, among which the most prominent can be the analysis of flow patterns developed as a result of the rotation and geometry of the individual screw element pairs. In this work the process design space identified at a small scale was further studied and scaled up to the pilot and production scales using in silico tools. This was achieved by 3D Smoothed Particle Hydrodynamics (SPH) simulations of individual screw elements that comprise the screw configuration and reduced-order 1D HME process simulations. The 1D HME simulations guided the process setup and scale-up by providing process maps for different experimental permutations. Process understanding generated through this approach allowed rapid process scale-up, in a sustainable manner by minimizing the number of actual experiments and the API use.
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