Self-emulsifying drug delivery systems (SEDDS), whereby drugs are dispersed in an oil–surfactant mix that emulsifies on contact with water, represent a highly promising approach for enhancing oral bioavailability. However, the choice of formulation is, at present, largely empirical both in terms of the composition dependence of the emulsification process and the solubilisation of the drug in the initial oil–surfactant mixture. In this investigation, a range of chemically related self-emulsifying systems have been studied, based on the Labrafil family of polyglycolysed oils, using Tween 80 and Tween 20 as surfactants. The ease of emulsification, the particle size distribution and the appearance of the emulsion droplets were studied as a function of composition, while the solubility of danazol and mefenamic acid in the various oil–surfactant mixes was measured. It was noted that dilution of the emulsions led to apparent change in particle size distribution. The more hydrophilic oil–surfactant mixes showed a greater ease of emulsification and a lower particle size. It was also noted that multiple emulsions could be formed using systems of lower polarity. A linear relationship was observed between the hydrophile–lipophile balance (HLB) of the mix and the solubility of both danazol and mefenamic acid, with more hydrophilic mixes showing greater drug solubility values. The study has indicated that, within the range studied, more hydrophilic mixes tend to result in superior emulsification properties and greater drug solubility.