Transdermal permeation-enhancing activivity ofN-adamantyln-alkanamides for ibuprofen in the rabbit

FourN-adamantyln-alkanamides were prepared by amide, condensation reaction between amantadine and n-alkanoic acid. Their enhancing activity on the penetration of ibuprofen through rabbit skin from petrolatum ointment was evaluated in in-vivo experiment. The experiments showed that the compounds have a strong transdermal penetration-enhancing activity, and their activities were comparable with that of Azone. The measurements of the fluorescence polarization of DPH-labelled DPPC liposomes showed that these compounds considerablly decreased the phase transition temperature of the liposomes. The mechanism of the transdermal penetration-enhancing activity of the compounds was ascribed to the reduction of the resisitance to drug flux of the stratum corneum lipid layers due to the loose packing of the layers when the bulk head group of the enhancers inserts into the layers.