Development and Optimization of Apixaban-Loaded Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Enhanced Dissolution and Potential Oral Bioavailability

Abstract

Apixaban is an orally active, direct Factor Xa inhibitor used for the prevention and treatment of thromboembolic disorders. Its poor aqueous solubility may limit dissolution and consequently affect oral absorption. The present study aimed to develop and optimize an Apixaban-loaded Self-Nanoemulsifying Drug Delivery System (SNEDDS) using suitable lipid excipients and a Quality-by-Design approach to improve its dissolution characteristics. Solubility screening identified Capryol® 90, Kolliphor® RH40, and Transcutol® P as suitable oil, surfactant, and co-surfactant, respectively. A pseudo-ternary phase diagram was constructed, and a 2:1 Smix ratio was selected based on the largest nanoemulsion region. A Box–Behnken Design comprising 17 experimental runs was employed, with droplet size, polydispersity index (PDI), and drug release selected as responses. Numerical optimization predicted an optimized composition of 20% Capryol® 90, 55% Kolliphor® RH40, and 25% Transcutol® P, with a desirability of 0.987. The optimized formulation exhibited a droplet size of 118.32 ± 2.14 nm, PDI of 0.214 ± 0.01, zeta potential of −24.86 ± 1.12 mV, and drug content of 99.12 ± 0.56%. In vitro dissolution studies demonstrated 95.84 ± 1.35% drug release from the optimized SNEDDS at 60 min compared with 72.48 ± 1.28% for pure Apixaban. The dissolution data showed the best fit to the Korsmeyer–Peppas model (R² = 0.9968; n = 0.47). The optimized formulation also demonstrated good thermodynamic and accelerated stability over 3 months. Overall, the developed Apixaban-loaded SNEDDS significantly improved the in vitro dissolution performance of Apixaban and represents a promising approach for enhancing its oral delivery. Further in vivo pharmacokinetic studies are required to confirm improvement in oral bioavailability.