Matrix erosion is unavoidable during the release of poorly soluble drugs from gastric floating delivery system (GFDDS), which shortens the floating time and diminishes drug release. We fabricated a core-shell system (CSS) consisting of a low-density drug-loaded shell and a floating core using multi-nozzle semi-solid extrusion (SSE) 3D printing technology. The clarithromycin (CAM) loading capacity of the shell was 81.7%. The floating core paste provided structural support during printing and formed a hollow structure in CAM CSS, which increased the buoyancy in the early stage of drug release. In addition, the floating core had numerous micro-airbags that swelled when the solution penetrated the core, and generated CO. The micro-airbag structure and CO generation further increased the buoyancy of CSS. The CAM CSS achieved 74.5% (w/w) drug loading, 8 h sustained release, and immediate and prolonged floating (>10 h). This structure of CSS and floating core provide a novel perspective for constructing a stable gastric floating drug delivery system.
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