Tunable Drug Release from 3D-Printed Bilayer Tablets: Combining Hot-Melt Extrusion and Fused Deposition Modeling

This study presents a practical and tunable 3D printing-based approach for manufacturing oral controlled-release bilayer tablets by modulating drug release solely through layer ratio control within a single dosage form. Theophylline-loaded filaments were prepared via hot-melt extrusion (HME) using Kollicoat^® IR or hydroxypropyl cellulose as polymer matrices. The mechanical properties of the manufactured filaments were evaluated and compared with commercial filaments to confirm their suitability for fused deposition modeling (FDM) printing. Physicochemical characterization using scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy indicated partial crystallinity and molecular dispersion of the drug within the polymer matrices. Using a dual-nozzle FDM 3D printer, five bilayer tablets composed of two drug-loaded filaments at different layer ratios were successfully fabricated without altering formulation composition or processing conditions. Drug release studies revealed distinct dissolution behaviors that were strongly dependent on the bilayer composition. Overall, this study demonstrates that controlled drug release can be effectively achieved through geometric modulation of bilayer structures using a combined HME-FDM 3D printing approach, providing a practical platform for personalized oral drug delivery without increasing formulation complexity.