AZONE(R) AND THE FORMATION OF REVERSED MONOCONTINUOUS AND BICONTINUOUS LIPID-WATER PHASES

The interfacial properties of the skin penetration enhancer Azone(R) were investigated as well as the effect the substance has on the phase behaviour of two bilayer forming lipid-water systems, i.e., lecithin-water and monoolein-water. Interfacial studies revealed a change in Azone packing on the water surface as the area per molecule decreased below 62 angstrom2. It is suggested that this change reflects a situation where the polar amide bond of Azone loses its direct contact with water and the molecule adopts a straighter conformation normal to the surface. Phase studies show that Azone promotes the formation of reversed types of lipid-water phases such as bicontinuous cubic, reversed hexagonal and reversed micellar phases. From this phase behaviour and recent literature data, we suggest that the formation of reversed types of phases should be considered as one important mechanism behind the increased skin penetration of drugs caused by lipophilic substances such as Azone.