The objective of this study was to investigate if the increase in apparent solubility induced by liposomalization or micellization of the poorly soluble drug hydrocortisone (HC) would lead to an enhancement of its permeability through biological membranes. For this purpose phosphatidylcholine liposome formulations as well as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelle dispersions and polyvinylpyrrolidone (PVP) supersaturated solutions were prepared in order to increase the apparent solubility of HC. Both the apparent solubility of hydrocortisone (i.e. amount of drug entrapped plus non-entrapped in the carriers) as well as the concentration of molecularly dissolved drug (i.e. fraction non-entrapped into carriers, truly molecularly dissolved fraction) were characterized. Subsequently, the permeability of hydrocortisone was assessed for each type of formulation using the in vitro sheep nasal mucosa permeability assay. In all formulations where solubilizing agents are present, an enhanced flux of HC (compared to the pure drug powder suspension) is observed. The expected linear correlation between apparent solubilities and fluxes was not found, whereas, the concentrations of molecularly dissolved HC were found to be directly proportional to the respective fluxes. This is an experimental proof for the hypothesis that, of all the strategies to increase the apparent solubility of poorly soluble drugs, enhancement of the molecularly dissolved drug concentration (induction of true supersaturation) would lead to better permeation though membranes.