Development, Optimization Using Box–Behnken, In Vitro, Ex Vivo Characterization & Pharmacokinetic Evaluation of Elagolix Sodium Loaded Self-Nano Emulsifying Drug Delivery System

Elagolix sodium is a novel, orally active non-peptide GnRH receptor antagonist used to treat endometriosis and uterine fibroids, as a BCS class III drug, it exhibits high solubility but low permeability, leading to poor and variable oral absorption. Limited permeability restricts bioavailability, but strategies such as lipid-based systems (nanoemulsions, SEDDS/SNEDDS), solid lipid or nanostructured lipid nanoparticles (SLN/NLC), permeation enhancers and cyclodextrin complexes can enhance oral absorption. The current research focused on the formulation and optimization of a self-nanoemulsifying drug delivery system (SNEDDS) for elagolix sodium aims to overcome low permeability and enhance its oral bioavailability. ELAG-SNEDDS were prepared using Labrafil M2125 CS, Tween 80, and Transcutol P at various ratios (1:1 to 4:1), and nanoemulsion region was determined using pseudo-ternary phase diagrams. The evidence from our research shows that optimized ELAG-SNEDDS was stable under thermodynamic conditions and possessed a droplet size of 216.8 ± 1.044 nm, zeta (ζ) potential − 38.04 ± 0.372 mV, exhibited a PDI of 0.439 ± 0.024 and time of emulsification < 1 minute. In pharmacokinetic study, ELAG-SNEDDS substantially increased drug absorption in the female Sprague Dawley (SD) rats, producing a higher C _max and lower T _max compared with the raw drug. These early outcomes suggest that ELAG-SNEDDS has the potential to serve as an effective delivery system of improving the permeability, absorption and oral bioavailability of elagolix sodium and may offer therapeutic potential in the treatment of endometriosis.