Toward high-resolution 3D-printing of pharmaceutical implants - A holistic analysis of relevant material properties and process parameters.

In this work, filament-based 3D-printing, the most widely used sub-category of material extrusion additive manufacturing (MEAM), is presented as a promising manufacturing platform for the production of subcutaneous implants. Print nozzle diameters as small as 100 µm were utilized demonstrating MEAM of advanced porous internal structures at the given cylindrical implant geometry of 2 mm × 40 mm. The bottlenecks related to high-resolution MEAM of subcutaneous implants are systematically analyzed and the print process is optimized accordingly. Custom synthesized biodegradable phase-separated poly(ether ester) multiblock copolymers exhibiting appropriate melt viscosity at comparatively low printing temperatures of 135 °C and 165 °C were utilized as 3D-printing feedstock. The print process was optimized to minimize thermomechanical polymer degradation by employing print speeds of 30 mm∙s-1 in combination with a nozzle diameter of 150 µm at layer heights of 110 µm. These results portray the basis for further development of subcutaneous implantable drug delivery systems where drug release profiles can be tailored through the adaption of the internal implant structure, which cannot be achieved using existing manufacturing techniques.

Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders.

Tribo-charging is often a root cause of mass flow deviations and powder adhesion during continuous feeding. Thus, it may critically impact product quality. In this study, we characterized the volumetric (split- and pre-blend) feeding behavior and process-induced charge of two direct compression grades of polyols, galenIQ™ 721 (G721) for isomalt and PEARLITOL® 200SD (P200SD) for mannitol, under different processing conditions. The feeding mass flow range and variability, hopper end fill level, and powder adhesion were profiled. The feeding-induced tribo-charging was measured using a Faraday cup. Both materials were comprehensively characterized for relevant powder properties, and their tribo-charging was investigated for its dependence on particle size and relative humidity. During split-feeding experiments, G721 showed a comparable feeding performance to P200SD with lower tribo-charging and adhesion to the screw outlet of the feeder. Depending on the processing condition, the charge density of G721 ranged from -0.01 up to -0.39 nC/g, and for P200SD from -3.19 up to -5.99 nC/g. Rather than differences in the particle size distribution of the two materials, their distinct surface and structural characteristics were found as the main factors affecting their tribo-charging. The good feeding performance of both polyol grades was also maintained during pre-blend feeding, where reduced tribo-charging and adhesion propensity was observed for P200SD (decreasing from -5.27 to -0.17 nC/g under the same feeding settings). Here, it is proposed that the mitigation of tribo-charging occurs due to a particle size-driven mechanism.