Theoretical and experimental studies of transport of micelle-solubilized solutes

A physical model describing the simultaneous diffusion of free solute and micelle-solubilized solute across the aqueous boundary layer, coupled with partitioning and diffusion of free solute through a lipoidal membrane, is derived. In vitro experiments utilizing progesterone and polysorbate 80 showed excellent agreement between theoretical predictions based on independently determined parameters and experimental results. The physical model predicts that micelles can assist the transport of solubilized solute across the aqueous diffusion layer, resulting in a higher solute concentration at the membrane surface than would be predicted if micelle diffusion is neglected. At high surfactant concentrations, the aqueous diffusion layer resistance can be eliminated and the activity of the solute at the membrane can approach the bulk solute activity. This mechanism could explain observed enhanced absorption rates in vivo when both micelle solubilization occurs and the aqueous diffusion layer is an important transport barrier. The importance of determining and defining the thermodynamic activity of the diffusing solute is emphasized.