Can filaments, pellets and powder be used as feedstock to produce highly drug-loaded ethylene-vinyl acetate 3D printed tablets using extrusion-based additive manufacturing?

Highlights

• The mechanical and rheological properties are limiting steps for FFF.

• Increasing the VA content showed lower buckling stress, elastic and flexural modulus.

• The inadequate flow during FFF was due to the viscosity variation during extrusion.

• DEAM showed formulation freedom as the screw rotation drives the material flow.

• In-vitro kinetics was similar between tablets printed from filaments, pellets or powder.

Personalized medicine, produced through 3D printing, is a promising approach for delivering the required drug dose based on the patient’s profile. The primary purpose of this study was to investigate the potential of two different extrusion-based additive manufacturing techniques – fused filament fabrication (FFF) and screw-based 3D printing, also known as direct extrusion additive manufacturing (DEAM). Different ethylene-vinyl acetate (EVA) copolymers (9 %VA, 12 %VA, 16 %VA, 18 %VA, 25 %VA, 28 %VA, and 40 %VA) were selected and loaded with 50% (w/w) metoprolol tartrate (MPT). Hot-melt extrusion was performed to produce the drug-loaded filaments.

These filaments were used for FFF in which the mechanical and rheological properties were rate-limiting steps. The drug-loaded filament based on the 18 %VA polymer was the only printable formulation due to its appropriate mechanical and rheological properties. As for the highest VA content (40 %VA), the feeding pinch rolls cause buckling of the filaments due to insufficient stiffness, while other filaments were successfully feedable towards the extrusion nozzle. However, poor flowability out of the extrusion nozzle due to the rheological limitation excluded these formulations from the initial printing trials. Filaments were also pelletized and used for pellets-DEAM. This method showed freedom in formulation selection because the screw rotation drives the material flow with less dependence on their mechanical properties.

All drug-loaded pellets were successfully printed via DEAM, as sufficient pressure was built up towards the nozzle due to single screw extrusion processing method. In contrast, filaments were used as a piston to build up the pressure required for extrusion in filament-based printing, which highly depends on the filament’s mechanical properties. Moreover, printing trials using a physical mixture in powder form were also investigated and showed promising results. In vitro drug release showed similar release patterns for MPT-loaded 3D printed tablets regardless of the printing technique. Additionally, pellets-DEAM enabled the production of tablets with the highest VA content, which failed in FFF 3D printing but showed an interesting delayed release profile.

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Aseel Samaro, Bahaa Shaqour, Niloofar Moazami Goudarzi, Michael Ghijs, Ludwig Cardon, Matthieu N. Boone, Bart Verleije, Koen Beyers, Valérie Vanhoorne, Paul Cos, Chris Vervaet,
Can filaments, pellets and powder be used as feedstock to produce highly drug-loaded ethylene-vinyl acetate 3D printed tablets using extrusion-based additive manufacturing?, International Journal of Pharmaceutics, Volume 607, 2021, 120922, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2021.120922.