Synergistic gastric retention of rebamipide via hollow bioadhesive microspheres for enhanced ulcer therapy

To address the low oral bioavailability and frequent dosing requirement of rebamipide, this study developed hollow bioadhesive microspheres based on a synergistic gastroretentive mechanism. The formulation utilizes ethyl cellulose/ Eudragit® EPO as the matrix to achieve buoyancy and is modified with a glyceryl monooleate coating to impart bioadhesion. The optimized microspheres exhibited a regular morphology, demonstrating excellent sustained floating and mucoadhesive properties in vitro. Animal studies confirmed significantly prolonged gastric residence time. Pharmacokinetic analysis revealed a 226% increase in relative bioavailability compared to commercial tablets. In an ethanol-induced gastric ulcer rat model, the system effectively reduced ulcer indices by prolonging local drug exposure, and showed comprehensive therapeutic effects, including anti-inflammatory, antioxidant, and enhanced mucosal defense activities, with no observed significant toxicity. This study provides an effective and safe drug delivery strategy for the local and sustained treatment of gastric ulcers.