This study describes the evaluation and characterization of a self-nanoemulsifying drug delivery system (SNEDDS) consisting of a nonionic surfactant (Cremophor RH40), a mixture of long chain mono-, di-, and triacylglycerides (Maisine 35-1 and Sesame oil) and ethanol. Compositions containing 10% (w/w) ethanol, 40%-60% (w/w) lipid content, and 30%-50% (w/w) Cremophor RH40 were identified as pharmaceutically relevant, robust, and self-nanoemulsifying when dispersed in aqueous media. The influence of adding three different lipophilic model drug compounds (danazol, halofantrine, and probucol) to the SNEDDS was evaluated. While danazol precipitated from the SNEDDS after dispersion in aqueous media, halofantrine and procubol remained solubilized. Halofantrine- and procubol-loaded SNEDDS were evaluated in both saline and in media simulating fasted and fed-state intestinal fluid (FaSSIF and FeSSIF) using dynamic light scattering and small-angle X-ray scattering (SAXS) techniques. Stable nanoemulsions with droplet sizes in the range of 20-50 nm were formed in all media and with and without drugs. The mean size of the droplets was neither affected significantly by being dispersed into the media simulating gastro intestinal fluid, nor by addition of the drug. (c) 2007 Wiley-Liss, Inc.