The level of solubilization of the drug testosterone propionate into 2% w/w oil-in-water (o/w) microemulsions, stabilized by the nonionic surfactant polyoxyethylene 10-oleyl ether (Brij 96) and containing a range of oils, has been determined. Although testosterone propionate was readily soluble in the ethyl esters ethyl oleate, ethyl caprylate, and ethyl butyrate, and the triglycerides soybean oil, Miglyol 812, and tributryin, and the alkene 1-heptene, only microemulsions containing the ethyl esters and the triglyceride oils exhibited a significant increase in solubilization over the corresponding micellar solution (i.e., surfactant solution in the absence of oil). Furthermore, the increase in drug solubility observed in the microemulsion systems was not related to the solubility of the drug in the bulk oil. That is, while the smaller molecular volume oils, such as ethyl butyrate, exhibited a greater capacity for the drug, microemulsions containing these oils were only marginally better at solubilizing the drug than the corresponding micellar solution. In contrast, microemulsions containing the larger molecular volume oil, Miglyol 812, gave levels of drug solubilization almost three times those containing ethyl butyrate, yet the bulk capacity for drug in this oil was less than half that of ethyl butyrate. Light scattering and phase inversion temperature studies suggested that the structure of the microemulsion was sensitive to the oil being used, in that, at the low oil concentrations used in this study, the smaller molecular volume oils generally penetrated the interfacial surfactant monolayer in much the same way as a cosurfactant, causing an alteration, presumably a dilution, of the relatively concentrated polyoxyethylene region close to the hydrophobic core, thereby destroying one of the main loci of drug solubilization and counteracting any advantages encountered due to the high solubility of the drug in the bulk oil.
