Menthol-based self microemulsifying drug delivery system for augmented intestinal absorption of edoxaban

Abstract

BACKGROUND: Clinical effectiveness of edoxaban is hindered by poor solubility and limited permeability due to P-glycoprotein (P-gp) efflux. AIM: The aim was to hasten dissolution and intestinal permeability of edoxaban by loading into microemulsion system consisting of menthol as oil and inhibitor of P-gp. METHODS: Pseudo-ternary phase diagram was constructed at 37°C and microemulsion comprising menthol, tween 80, ethanol and water at ratio of 20:30:30:20 was selected and evaluated. RESULTS: Microemulsion's droplet size was 163.47 nm, its polydispersity index was 0.28, and its zeta potential was -16.43 mV. Edoxaban was loaded in water-free system for dissolution testing. This system underwent self microemulsification in dissolution medium to increase dissolution efficiency to 95.39%, compared with 66.64% for unprocessed edoxaban. Stability assessments demonstrated the system's stability against various stress conditions. In situ intestinal perfusion studies indicated improved permeability, with 2.96-fold increase in the duodenum and 2.06-fold increase in the ileum compared with edoxaban in aqueous solution. This enhanced absorption was attributed to inhibition of P-gp-mediated efflux by menthol and Tween 80, as well as increased membrane fluidity and permeability. CONCLUSION: These encouraging outcomes highlight the potential of microemulsion in improving both solubility and intestinal permeability of edoxaban enhancing of its oral bioavailability and therapeutic effectiveness.