Purpose: This study aimed to design and characterize a novel dual-function floating-bioadhesive drug delivery system based on a hollow structure to extend gastroretentive time and enhance the bioavailability of ofloxacin. Methods: Hollow spherical shells were fabricated via fluidized-bed coating using a blended polymer film composed of (SuE (Surelease ® E-7-19040) and EuN (Eudragit ® NE 30D)). The system integrated a hollow spherical shell, a waterproof layer, a drug layer, a release-retarding ethylcellulose (EC) film, and an outer bioadhesive layer. The mechanical properties, in vitro floating and bioadhesive behavior, drug release profile, and in vivo pharmacokinetics were comprehensively evaluated. Results: The blended film at a SuE/EuN ratio of 4:4 exhibited optimal mechanical rigidity and strength for the hollow shell. Analysis of the release profile showed a zero-order release for the first 4 h, which was in accordance with the predicted value. The optimized formulation demonstrated excellent buoyancy with a floating rate of 96.3± 0.5% and 100% bioadhesion on gastric mucosa. In vivo pharmacokinetic studies in New Zealand rabbits revealed that the test formulation had a prolonged elimination half-life (6.65± 0.94 h) and a relative bioavailability of 112.2± 14.9% compared to the reference tablet. Conclusion: The developed floating-bioadhesive system successfully combined hollow-structure buoyancy with mucoadhesion to achieve prolonged gastric retention and sustained drug release, offering a feasible approach for gastroretentive drug delivery systems. The infographic illustrates a dual-function gastroretentive system: floating-bioadhesive. It includes a diagram of the gastrointestinal tract and a chemical structure with the text ’Narrow absorption window in upper GI tract, pH-dependent solubility.’ A cross-section of the system shows layers: bioadhesive layer, release retarding film, drug layer, waterproof layer and the hollowspherical shell. Below, a diagram indicates ’ 8h Floating rate: 96.3± 0.5 percent.’ A graph shows zero-order release (0-4h, R squared = 0.9982). Another diagram highlights ’Prolonged gastric retention, sustained drug release, enhanced bioavailability.’.Infographic on dual-function gastroretentive system: floating and bioadhesive pellets based on a hollow structure. Keywords: Hollow pellets, mechanical properties, floating, bioadhesive ability, bioavailability
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