Dual-extruder 3D-printing of biodegradable subcutaneous implants for controlled drug delivery

Subcutaneous implantable drug delivery systems (SIDDS) offer significant reduction in administration frequency compared to oral dosage forms, which improves patient adherence. However, current manufacturing methods, such as hot melt extrusion, offer limited flexibility for individualizing product specifications (e.g., changes in drug loading or changes in the daily dose) and for providing on-demand solutions. Here, dual-extruder fused filament fabrication was explored for the first time as an advanced manufacturing method to produce biodegradable, drug-loaded SIDDS with customizable release profiles. Seven advanced implant designs (including monolithic and core-shell type implants) were tested to study the impact of 3D-printing parameters (e.g., the internal porosity or shell thickness) on the drug release profile, confirming the suppression of burst release and the achievement of zero-order or tri-phasic release profiles. The implants were further characterized with respect to quality parameters such as shell continuity, shell thickness, and drug content. Overall, this work provides a fundamental framework to produce SIDDS with adaptable release profiles and release time frames through adjustment of 3D-printing parameters.