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.

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The incorporation of testosterone and two of its esters, and progesterone and one of its esters (log Poct varying from 3.3 to 6.9) into 2% w/w soybean oil/Brij 96 microemulsions and Brij 96 surfactant systems has been examined. Possible sites of incorporation have been investigated. The drug carrying improvement of an oil-in-water microemulsion over a micellar system appears to depend on the solubility of the drug in the dispersed oil phase and is significant only for very lipophilic drugs.

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The ease of preparation, thermodynamic stability, optical transparency and ability to sterilise by filtration renders microemulsion systems an attractive prospect for use in d r q delivery. In this investigation we attempt to determine whether these systems offer advantages over micellar preparations in the formulation of poorly water soluble drugs.We compare the incorporation of a model poorly water soluble drug, diazepam (log P =2.6), in both micellar solutions of polyoxyethylene-10-oleyl ether (Brij 96), and in O/W microemulsion systems consisting of 2%w/w soyabean oil, with varying concentrations of Brij 96. The microemulsion systems were clear (disperse phase droplets less than 30nm), non-birefringent and stable before and after the addition of diazepam. Solubilities were determined by stirring a known excess of diazepam into each sample and allowing equilibrium to be achieved in a shaking water bath at 25OC for 8 days. The samples were then passed through a 0.22um filter and the concentration of the resulting clear preparations determined by dilution with OS%w/v sulphuric acid in methanol and subsequent absorbance readings taken at 284nm. 1- .A 2% soyabean oil microemulsion 0 micellar solution The similarity in the amount incorporated in both types of systems may be explained b Y consideration of the site of solubilisation. This has been studied using dimethoxytetraethylene glycol (DMTG) / water mixtures, in which pure DMTG is chosea to represent the local environment of dehydrated polyoxyethylene (Patel et a1 (1981)).Results show an exponential increase in diazepam solubility with increasing DMTG. Thisindicates that the major site of diazepam incorporation in both microemulsion and micellar systems is the region of concentrated, dehydrated polyoxyethylene chains that occurs close to the oil or hydrocarbon core.It therefore appears that unless a drug has significant solubility in the dispersed oil phase of a microemulsion these systems offer little advantage over micellar ones for increadG the amount of drug which can be incorporated.Patel, M.S. et a1 (1981) J. Pharm. Pharmacol. 33(suppl.): 64P