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

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.