IN VITRO AND IN VIVO EVALUATION OF RABEPRAZOLE-LOADED β-CYCLODEXTRIN NANOSPONGES FOR ENHANCED ANTI-ULCER ACTIVITY

Awinish Kumar Shrivastaw*, Manju Makhija

Rabeprazole is a widely prescribed proton pump inhibitor for the treatment of gastric ulcer and other acid-related disorders. However, its poor aqueous solubility, acid instability, and limited oral bioavailability restrict its therapeutic effectiveness. The present study aimed to evaluate the in vitro performance and in vivo anti-ulcer efficacy of an optimized rabeprazole-loaded β-cyclodextrin nanosponge formulation (F5). The optimized formulation was filled into hard gelatin capsules and evaluated for pharmaceutical quality, in vitro dissolution, release kinetics, stability, and anti-ulcer activity. The capsules complied with pharmacopoeial quality requirements and exhibited a sustained drug release profile with 98.42 ± 1.11% cumulative drug release over 12 h. Drug release followed diffusion-controlled kinetics, with the Higuchi model providing the best fit, while the Korsmeyer–Peppas model indicated an anomalous (non-Fickian) release mechanism. The anti-ulcer activity was evaluated using an ethanol-induced gastric ulcer model in Wistar rats. The optimized nanosponge formulation significantly reduced the ulcer index from 8.72 ± 0.41 in the ulcer control group to 0.94 ± 0.11, corresponding to 89.22% gastroprotection (p < 0.001). In addition, the formulation restored gastric pH (3.82 ± 0.09) and markedly improved gastric histological architecture by reducing mucosal erosion, inflammatory cell infiltration, and epithelial damage. Stability studies demonstrated only minor changes in particle size, polydispersity index, entrapment efficiency, drug loading, and cumulative drug release after storage, indicating satisfactory physicochemical stability. Overall, the findings demonstrate that β-cyclodextrin nanosponges represent an effective oral drug delivery platform for rabeprazole by providing sustained drug release, improved stability, and enhanced anti-ulcer efficacy, highlighting their potential for the improved management of gastric ulcer disease.