Self-Nanoemulsifying Drug Delivery System for Enhanced Bioavailability and Improved Hepatoprotective Activity of Biphenyl Dimethyl Dicarboxylate

Abstract

Biphenyl Dimethyl Dicarboxylate (BDD) is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-nanoemulsifying drug delivery system (SNEDDS) containing BDD has been successfully prepared using carefully selected ingredients which are less affected by pH and ionic strength changes to improve its bioavailability. SNEDDS is an isotropic mixture of lipid, surfactant, and cosurfactant which are spontaneously emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo ternary phase diagrams composed of various excipients were plotted to identify self -nano -emulsifying area. Droplet size changes upon dilution with aqueous media and in vitro release of BDD from SNEDDS in 0.1N HCl and phosphate buffer (pH 7.4) were studied and compared with commercial chinese pilules and Pennel capsules. The hepatoprotective activity upon oral administration of SNEDDS against carbon tetrachloride-induced oxidative stress in albino rats was assessed by measuring biochemical parameters like serum glutamic oxalacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH). Results showed that using a proper ratio of Tween 80 to Transcutol as surfactant and co-surfactant respectively and Miglyol 812 as oil to surfactants mixture resulted in production of infinitely diluted formulations in nano droplet size range. BDD self nano emulsified formula composed of 20% Miglyol 812, 60% Tween 80 and 20% Transcutol released 99% of the drug very rapidly within 10-15 minutes regardless of the pH condition. The oral absorption and bioavailability of BDD self nano emulsified formula in albino rats were significantly enhanced (P<0.01) with an average improvement of 1.7 and 6-folds that of commercial chinese pilules and Pennel capsules respectively. This improvement was also confirmed histopathologically in chemically injured rats and by the significant decrease in elevated liver enzymes level.