Screening of pharmaceutical polymers for extrusion-Based Additive Manufacturing of patient-tailored tablets.

Abstract

The main objective of this work was to explore the potential of coupling hot-melt extrusion (HME) to Fused Filament Fabrication (FFF), also known as Extrusion-Based Additive Manufacturing (EBAM) or 3D Printing, in order to manufacture 3D printed tablets with different release behavior from plasticizer-free filament matrices. The suitability of different thermoplastic polymers towards FFF was investigated, and a link between the mechanical properties of filaments produced by HME and the feeding performance into the FFF printer was established. Model drugs with different aqueous solubility (metoprolol tartrate and theophylline anhydrous) were processed with hydrophilic and hydrophobic polymers, and the influence of the formulation, drug concentration and applied process settings on the release kinetics was investigated. Filaments with up to 40% drug load were successfully extruded with a smooth surface and a diameter of 1.75±0.05mm. However, filaments with high brittleness and low toughness were broken by the feeding gears. In contrast, none of the filaments were squeezed aside by the gears, which indicated that they were sufficiently stiff as indicated by the high Young's moduli of all formulations. For all formulations, the release from the tablets with 50% infill degree was faster as compared to the tablets with 100% infill degree. Theophylline (20% w/w) release from Kollicoat® IR matrix was completed within 40min from 50% infill tablets. In contrast, 80% metoprolol tartrate was released from the hydrophobic Capa® 6506 polymer within 24hrs from 50% infill 3D tablets containing 40% w/w MPT.