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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Edoxaban's clinical efficacy is limited by poor solubility and P-glycoprotein (P-gp) mediated efflux, reducing its oral absorption.
• Developing strategies to overcome these barriers is crucial for enhancing edoxaban's therapeutic potential.

Purpose of the Study:

• To enhance the dissolution and intestinal permeability of edoxaban using a microemulsion system.
• To incorporate menthol as both an oil phase component and a P-gp inhibitor within the microemulsion.

Main Methods:

• Construction of a pseudo-ternary phase diagram at 37°C to identify optimal microemulsion formulations.
• Selection and evaluation of a microemulsion composed of menthol, Tween 80, ethanol, and water (20:30:30:20 ratio).
• Characterization of microemulsion properties including droplet size, polydispersity index, and zeta potential.

Main Results:

• The optimized microemulsion exhibited a droplet size of 163.47 nm, PDI of 0.28, and zeta potential of -16.43 mV.
• Self-microemulsification in dissolution media increased edoxaban's dissolution efficiency to 95.39% (vs. 66.64% for unprocessed drug).
• In situ intestinal perfusion studies showed a 2.96-fold increase in duodenal and 2.06-fold increase in ileal permeability, attributed to P-gp inhibition and enhanced membrane fluidity.

Conclusions:

• The developed microemulsion system effectively improves edoxaban's solubility and intestinal permeability.
• This approach holds significant potential for enhancing edoxaban's oral bioavailability and overall therapeutic efficacy.
• Menthol and Tween 80 play a key role in inhibiting P-gp efflux and facilitating drug absorption.