<![CDATA[Oxidative stress is implicated in ageing and a range of degenerative disorders, and quercetin is a flavonol with well-documented radical-scavenging activity. Its pharmaceutical use is nevertheless limited because it belongs to class II of the Biopharmaceutics Classification System, with low aqueous solubility. A self-nanoemulsifying drug delivery system (SNEDDS) keeps such a compound molecularly dissolved in an isotropic oil–surfactant–cosurfactant mixture that disperses spontaneously into a nanoemulsion. To optimise the proportions of oleic acid, Tween 80 and PEG 400 in a quercetin SNEDDS and to verify the physical characteristics and antioxidant activity of the optimum formula. A laboratory experimental study using a D-optimal mixture design in Design-Expert® version 13, with oleic acid 10–20%, Tween 80 70–80% and PEG 400 10–20% constrained to a total of 100%, generating 16 runs. Preconcentrates were sonicated, homogenised, saturated with quercetin and centrifuged. Responses were drug load, emulsification time, particle size, polydispersity index, transmittance, zeta potential and DPPH IC₅₀. Quercetin was quantified by a validated UV-Vis method at 373 nm. Numerical optimisation minimised particle size, emulsification time, polydispersity index and IC₅₀ while maximising drug load, and the optimum formula was verified in triplicate. Responses varied widely across the 16 runs: drug load 1.043–16.755 mg/mL, emulsification time 18.6–34.8 s, particle size 90–220 nm, polydispersity index 0.138–0.245, transmittance 90.106–99.379%, zeta potential −20.5 to −38.0 mV and IC₅₀ 40.49–146.13 ppm. All five optimisation models were significant (p < 0.05) with non-significant lack of fit. Raising the oleic acid proportion enlarged droplets, lengthened emulsification and widened the size distribution, whereas Tween 80 acted in the opposite direction. The optimum formula was oleic acid 10%, Tween 80 80% and PEG 400 10%, with a desirability of 0.898. Verification gave a particle size of 90 ± 5 nm, polydispersity index 0.138 ± 0.006, drug load 13.377 ± 0.554 mg/mL and IC₅₀ 67.637 ± 0.957 ppm, none differing significantly from prediction (p > 0.05; prediction errors ≤ 0.85%). The optimised quercetin SNEDDS forms a nanometric, homogeneous and rapidly self-emulsifying system with strong antioxidant activity, and the mixture model is sufficiently predictive to guide further development.]]>
