Pullulan-based self-nanoemulsifying granules: A functional carbohydrate matrix for stabilizing and modulating the...

Pullulan, a water-soluble and food-grade polysaccharide with excellent film-forming and redispersibility properties, was investigated as a matrix-forming biomacromolecule to solidify a self-nanoemulsifying drug delivery system (SNEDDS) into self-nanoemulsifying granules (SNEGs) suitable for oral delivery. In contrast to conventional adsorption-based solid SNEDDS systems that rely on porous inorganic carriers, this approach utilizes a polymeric matrix entrapment strategy to incorporate a food-grade SNEDDS (fish oil, Tween 80, and PEG 400) into pullulan at varying ratios (1:0.5, 1:0.75, and 1:1 w/w). The optimized liquid PSNEDDS exhibited nanoemulsion characteristics with droplet sizes of 13-16 nm and high optical clarity (>80% transmittance). Following solidification, the pullulan-based SNEGs formed free-flowing granules that rapidly reconstituted into transparent nanoemulsions, maintaining droplet sizes of 19-22 nm. Among the tested formulations, the intermediate pullulan-to-PSNEDDS ratio (1:0.75) achieved the most balanced performance in terms of granule integrity, redispersibility, and release behavior. Viscosity analysis of reconstituted systems suggested hydration-mediated diffusion consistent with anomalous transport kinetics. Quercetin was employed as a model hydrophobic compound to enable controlled and reproducible in vitro release evaluation. Sustained release behavior was observed across formulations while preserving nanoemulsion characteristics after storage under ambient, refrigerated, and frozen conditions. These findings demonstrate that pullulan functions not only as a solidifying excipient but also as a hydration-responsive polymeric matrix capable of modulating nanoemulsion release. This work establishes a carbohydrate-based solidification platform distinct from conventional silica-based systems and highlights the potential of pullulan-mediated nanoemulsion granules for delivering poorly water-soluble, plant-derived bioactives in food and nutraceutical applications.