A Modular Cavity-Based Soft Hydrogel for Floating and Controlled Drug Release via Additive Manufacturing

Abstract Extrusion-based additive manufacturing (AM) enables precise control over internal structure, providing opportunities to tailor geometry and transport behavior in soft material systems. Here, we report a 3D-printed, soft hydrogel-based gastroretentive floating system (GFDDS) that integrates structural design with sustained release functionality within a single construct. The formulation was systematically optimized for printability and floatability under simulated gastric conditions. Optimization through κ-carrageenan (KC) concentration and incorporation of freeze-dried vegetable fibers (FD-Veg) enabled reliable layer-by-layer fabrication while maintaining functional buoyancy for up to 5 days. Release behavior was evaluated using hydrophobic risperidone (RIS) and hydrophilic metoprolol tartrate (MT) as model drugs to investigate drug transport characteristics. The 3D-printed GFDDS comprising a single-phase hydrogel provided sustained RIS release over approximately 6 h. In contrast, hydrophilic MT was rapidly released within approximately 50 min. Incorporation of MT within a secondary hydrogel matrix extended its release to approximately 6 h, with a release duration similar to our PLGA-encapsulated MT benchmark. The modular cavity-based design allows midprint cavity drug loading and modification of release behavior through the addition of a secondary matrix without altering the printable formulation. This work presents a simplified strategy for modifying drug release in soft hydrogel systems through material formulation and on-demand AM processing.