Investigation of a biopolymer-based pH-responsive and sustained release raft-gel-forming tablet of famotidine: In-vitro, ex-vivo, bioavailability and anti-ulcer evaluation in New Zealand albino rabbit

Abstract

Famotidine (FAM), a histamine H2 receptor antagonist, routinely used for gastric ulcers. However, the poor permeability, short biological half-life and degradation in acidic gastric environment, limits its bioavailability and reduces the expression of potential bioactivity. The present study investigated sodium alginate as a pH responsive and raft-gel-forming biopolymer along with slowly releasing ingredients to achieve stomach site-specific, stable and sustained release FAM tablet (FAMRFT) for the management of gastric ulcer. The Box Behnken design was adopted to optimize raft strength and sustained release profile. The optimized FAMRFT was evaluated in terms of in-vitro, ex-vivo and in-vivo in suitable animal models. In-vitro release study showed that FAMRFT can effectively and continuously sustained-release with diffusion mechanism. Ex-vivo permeation study in porcine gastric mucosa showed two-fold increase in permeation parameters. In-vivo studies in New Zealand albino rabbits, the X-ray scintigraphy confirmed the formation of raft-gel in gastric and buoyancy, improved 3-fold bioavailability as compared to pure FAM and commercial tablet, respectively. Further, the improved gastro protective effects were reflected in gastric volume, total acid output, pH, ulcer score, ulcer index, ulcer protection and biomarkers level such as malondialdehyde (MDA), total glutathione (GSH) and nitric oxide (NO) in aspirin-induced gastric ulcers in albino rabbit. Moreover, histopathological study revealed the absence of epithelial erosion, submucosal edema and leucocytes infiltration in gastric mucosa. The results indicate that sodium alginate-based pH responsive raft-gel may be a new formulation for the application of FAM for the treatment of gastric ulcer.