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The objective was to develop a microemulsion formulation for the transdermal delivery of testosterone. Microemulsion formulations were prepared using oleic acid as the oil phase, Tween20 as a surfactant, Transcutol as cosurfactant, and water. The microemulsions were characterized visually, with the polarizing microscope, and by dynamic light scattering. In addition, the pH, conductivity (sigma) and viscosity (eta) of the formulations were measured. Moreover, differential scanning calorimetry and diffusion-ordered nuclear magnetic resonance spectroscopy were used to study the formulations investigated. Conductivity measurements revealed, as a function of the weight fraction of the aqueous phase, the point at which the microemulsion made the transition from water-in-oil to bicontinuous. Alterations in the microstructure of the microemulsions, following incorporation of testosterone, have been evaluated using the same physical parameters (pH, sigma and eta) and via Fourier-transform infrared spectroscopy (FT-IR), (1)H NMR and (13)C NMR. These methods were also used to determine the location of the drug in the colloidal formulation. Finally, testosterone delivery from selected formulations was assessed across porcine skin in vitro in Franz diffusion cells. The physical parameter determinations, combined with the spectroscopic studies, demonstrated that the drug was principally located in the oily domains of the microemulsions. Testosterone was delivered successfully across the skin from the microemulsions examined, with the highest flux achieved (4.6+/-0.6microgcm(-2)h(-1)) from a formulation containing 3% (w/v) of the active drug and the composition (w/w) of 16% oleic acid, 32% Tween20, 32% Transcutol and 20% water. The microemulsions considered offer potentially useful vehicles for the transdermal delivery of testosterone.

This research determined the uptake of individual components of topically applied microemulsions into the stratum corneum (SC) and assessed their molecular effects on skin barrier function. The microemulsions comprised oleic acid, Tween20, Transcutol and water. The effects of selected formulations, and of the individual components, on the conformational order of the SC intercellular lipids, and on SC hydration, were assessed by infrared spectroscopy. Measurements were made as a function of SC depth by progressively tape-stripping the membrane in the normal way. SC uptake of microemulsion components was quantified via extraction and analysis of the collected tape strips. SC hydration increased in proportion to the water content of the microemulsion. Each of the microemulsion components penetrated into the SC, but to different extents. Oleic acid decreased the conformational order of the SC lipids, and induced some phase separation, as revealed by the frequency shifts and peak areas of the absorbances associated with -CH(2) symmetric and asymmetric stretching vibrations. Tween20 extracted some of the SC intercellular lipids. In summary, SC structure was perturbed by all components of the microemulsions, and the degree of the effects detected was proportional to the level of the respective component present in the skin.

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