Oil-entrapped ranitidine HCl beads heal peptic ulcers via local and systemic mechanisms

Objective: Oral gastroretentive system is one of the site-specific drug delivery system, which is designed to be retained in upper GIT for a prolonged time. Ranitidine hydrochloride (RHCl), which is used frequently in treatment of peptic ulcer, is a suitable candidate for gastroretentive delivery systems. Dependently, floating oil-entrapped alginate beads of RHCl were developed and evaluated as an approach to site-specific delivery avoiding colonic degradation and enhancing both bioavailability and the proposed local effect.

Methods: Different formulations of floating beads were suggested and randomized using 2⁴ full factorial design. Optimized formulation was subjected for in vivo studies to measure the oral bioavailability and the healing effect of induced peptic ulcers.

Results: Beads size ranged from 1.32 to 2.3?mm. All beads revealed excellent floating capabilities. Optimum formulation (F12) has entrapment efficiency of 70%, drug loading of 7% and 71% RHCl released after 6?h. SEM of F12 shows a grossly spherical structure with presence of oil droplets distributed throughout structure. AUC obtained from F12 was nonsignificantly higher than that of a commercial tablet. Signs of ulcer healing appeared clearly with F12 through appearance of granulation tissue, collagen fibers and newly formed blood vessels. Healing rate and extent obtained with a commercial tablet were less than F12. Quantitative analysis confirmed histopathological findings.

Conclusion: Floating oil-entrapped beads are a promising approach for RHCl delivery to remain in stomach for a longer time ensuring site-specific delivery and consequently, enhancing local healing effect of peptic ulcers.