Quality-by-design optimization of CBD nanoemulsions : incorporating choline-based ionic liquids as sustainable surfactants

Abstract

A CBD-loaded NE was prepared using a choline-based IL as a stabilizing agent, with the same composition as the optimized formulation but replacing conventional surfactants by the IL: 1.5% MCT, 1.75% CBD and 1% IL. The formulation displayed a droplet size of approximately 125 nm and a low PDI of 0.156. After 24 hours, the NE retained its integrity, showing only slight variations in particle size and PDI, while maintaining a stable zeta potential of -38 mV and pH of 10.1. These findings indicate that choline oleate IL can serve as a promising alternative to conventional surfactants, providing comparable emulsifying performance. Despite IL-based systems typically yielding droplet sizes, promoting enhanced bioavailability and improved resistance to oxidation and hydrolysis due to the protective nature of the IL matrix in contrast to Span 80/Tween 80 nanoemulsions that tend to form larger droplets and show reduced stability under oxidative stress, the innovation and sustainability potential of NE-ILs still requires toxicological validation and regulatory clearance before large-scale implementation. Further studies are needed to evaluate its long-term stability and biopharmaceutical potential.