Augmentation of Permeability of Drugs having P-Glycoprotein Inhibition for Efficiency in Nocturnal Acid Breakthrough

Abstract

Purpose : Ranitidine is a BCS class III drug having low oral, lipophilicity and is susceptible to the Pglycoprotein (P-gp) efflux mechanism. Permeation enhancers enhance the bioavailability of ranitidine by increasing the partition coefficient (K oct/buffer there by increasing the lipophilicity and permeability. The main) aim of the present work is to overcome the problems of ranitidine bioavailability by expending permeation enhancers and P-gp inhibitors. Methodology : The existence of synergistic activity in permeation enhancement effect was studied using EDTA, citric acid, oleic acid, caprylic acid, sodium glycocholate and sodium deoxycholate. The P-gp inhibitor used here was felodipine, a first generation inhibitor showed P-gp inhibition activity at a concentration where it shows it pharmacological action. Three formulations were formulated and subjected to various physiochemical evaluations like weight variation, friability, hardness, drug content, in vitro drug release and kinetic studies.A continuous dissolution-absorption system was designed using everted intestine segment. Results : Synergistic effect in enhancing the permeability of ranitidine was found to exist between chelating agents in combination with fatty acids and its derivatives. From the precompression parameters data of the lubricated blend, it was found that the flow ability was good and can be compressed into tablets by direct compression method. The formulated ranitidine immediate release tablets exhibited first order release kinetics, resulting in rapid and complete release for two h. Conclusion : The effective drug permeability (P eff ) after three h or formulations TAB, TAB37, TAB37-PGP and TAB-MARK is 2.60, 3.17, 3.66 and 2.68, respectively. This shows that the permeability through chick intestine is more from TAB37-PGP by increased P-gp inhibition.