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 uitro 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 a t the membrane can approach the bulk solute activity. This mechanism could explain observed enhanced absorption rates in uiuo 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.
Keyphrase 0 Diffusion-transport of micelle-solubilized solutes, theoretical and experimental Solutes-micelle solubilized, transport, theoretical and experimental 0 Micelles-theoretical and experimental transport, solutes
The effects of micelle solubilization on the solubility and intestinal absorption of nonpolar solutes are well documented (1-8). Investigations have been performed to delineate the role of surfactants in diffusional transport. As a result of these studies, it is clear that several factors must be considered, such as the thermodynamic activity of the solute, diffusivities of the free solute and micelles, membrane permeability, and the importance of the aqueous diffusion layer in determining the overall transport rate.