Preparation of N-adamantyl n-alkanamides and evaluation of their transdermal penetration in the rabbit

Abstract Novel eight N-adamantyl n-alkanamides were synthesized by amide condensation reaction between amantadine and n-alkanoic acid(C 7 -C 13 ). Their enhancing activity on the penetration of salicylic acid through rabbit skin from petrolatum ointment was evaluated in in vivo experiment. The results of the experiment showed that the compounds have a strong transdermal penetration-enhancing activity, and their activity was parabolically dependent on the length of the alkyl chain. The mechanism of the transdermal penetration-enhancing activity of the compounds was ascribed to the reduction of the resistance to drug flux of the stratum corneum lipid layers due to the loose packing of the layers when the bulky head group of the enhancers inserts into the layers.