Computational Modeling for Regioselective Drug Delivery

Abstract

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