Process optimization of hot-melt extruded filaments for FDM 3D printing of personalized low-dose fludrocortisone...

Low-dose oral formulations are often associated with poor dose accuracy (mass and content non-uniformity) and limited reproducibility. Three-dimensional printing (3DP), particularly Fused Deposition Modeling (FDM), has emerged as a promising strategy to overcome limitations of conventional pharmaceutical compounding for oral therapies. FDM enables precise, digitally controlled deposition for decentralized, on-demand manufacturing at the Point of Care (PoC), but its implementation is limited by the availability of suitable pharmaceutical filaments. Especially at sub-percent drug loadings, achieving homogeneous drug distribution at such low concentrations is a major challenge. Fludrocortisone Acetate (FCA), a micronized corticosteroid administered at microgram daily doses and commonly compounded in Belgium in the absence of authorized products, was selected as a model drug. This study aimed to develop homogeneous low-dose (0.5% w/w) FCA-loaded filaments by Hot-Melt Extrusion (HME) suitable for FDM printing. The effects of adding 1% of a flow regulator (Aerosil® 200) and screw configuration (one vs. two kneading zones) on extrusion process parameters and drug distribution were investigated. Aerosil® 200 improved powder flow and feeding stability, and filament homogeneity resulted from the combined effect of formulation and screw configuration. Optimized filaments showed suitable mechanical properties for FDM and enabled printing of Immediate-Release (IR) oral dosage forms containing 50, 100, and 200 µg FCA. Printed waffle-shaped units complied with European Pharmacopoeia requirements for mass and content uniformity, hardness, and friability. Dissolution confirmed an IR profile, with > 80% FCA released within 45 min. This work demonstrates the feasibility of manufacturing pharmaceutically compliant low-dose dosage forms by combining HME and FDM, offering a reliable alternative to conventional compounding and advancing point-of-care personalized medicine.