Mixed monolayers of dipalmitoylphosphatidylcholine with Azone or oleic acid at the air-water interface

Abstract

The surface pressure-area characteristics of the skin penetration enhancers Azone ( N-dodecylazacycloheptanone) and oleic acid have been recorded as compression isotherms at 25 ° C of the pure films and in mixed monolayers with dipalmitoylphosphatidylcholine (DPPC). Holding the pure films at constant surface pressures revealed a slow dissolution of the Azone monolayers into the aqueous subphase compared with a negligible loss from the oleic acid and DPPC films. The mean area/molecule in the oleic acid mixtures followed the simple additivity rule but large expansions were evident in the case of the Azone mixtures. Both enhancers gradually reduced and finally abolished the liquid-expanded to liquid-condensed (LE/LC) phase transition of DPPC with increasing mole fraction and Azone was the more effective in this respect. Collapse pressures of the mixed films indicated miscibility of the components with evidence for the existence of an Azone-rich surface phase at high mole fractions. These results indicate the very clear differences in the effects exerted upon lipid packing by these two enhancers and the importance of the Azone head-group conformation to its activity. It is therefore likely that similar differences occur when these molecules interact with the lipid lamellae of the stratum corneum. The miscibility of lipids and enhancers is also a significant consideration in determining transport characteristics across the epidermis.