Structurally tuned drug release from hybrid manufactured tablets via overprinting and overmolding.

Hybrid manufacturing, which integrates three-dimensional printing and injection molding, presents a scalable solution for producing personalized oral dosage forms. This study presents a systematic comparison between overprinting and overmolding, two hybrid manufacturing strategies, to assess their influence on tablet microstructure, drug release dynamics, and processing performance. Using a Taguchi L9 experimental design, formulations containing polycaprolactone, poly(vinylpyrrolidone-co-vinyl acetate), and theophylline (5-30% w/w) were processed via hot-melt extrusion and fabricated into bilayer tablets using either overprinting or overmolding. Characterization techniques such as infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, oscillatory rheology, scanning electron microscopy, and micro-computed tomography revealed that overprinted tablets retained the porous structure of the printed layer, which facilitated faster drug release governed by Fickian diffusion. Overmolded tablets exhibited structural compaction due to molten polymer infiltration, reducing porosity and shifting release towards anomalous, diffusion-relaxation-controlled mechanisms. Drug release was primarily influenced by design parameters in overprinted tablets, whereas drug loading dominated performance in overmolded systems. The optimal filament formulation was identified at 15% drug loading, balancing molecular dispersion and mechanical stability. Kinetic modelling using the Korsmeyer-Peppas equation confirmed distinct release mechanisms between the two approaches. Additional structural modifications, such as solid barrier layers, modulated surface integrity and defect formation under prolonged exposure. These findings position overprinting as a platform for personalized, design-driven drug release, while overmolding offers robustness and controlled, sustained delivery. Together, these hybrid techniques provide complementary tools for advancing individualized pharmaceutical manufacturing.