Simple alkyl esters as skin permeation enhancers

Abstract

The use of simple alkyl esters, in particular ethyl acetate, as skin permeation enhancers for drugs is presented. Ethyl acetate was found to increase the transdermal flux of levonorgestrel, estradiol, hydrocortisone, 5-fluorouracil, and nifedipine through rat skin in vitro relative to that when ethanol or water were used as reference solvents. Relative to water, the flux of levonorgestrel was increased 80 fold using pure ethyl acetate. Relative to pure ethanol as a reference permeation enhancer, the flux of levonorgestrel was increased 12 to 15 fold using either pure ethyl acetate or volume fractions of ethyl acetate in ethanol down to 0.18 as permeation enhancers. Butyl acetate was also tested with levonorgestrel and was found to increase the flux about 7 fold relative to pure ethanol. The fluxes of estradiol, hydrocortisone, 5-fluorouracil, and nifedipine were increased from 75 to 650 fold, depending on the drug, when ethyl acetate was used as a permeation enhancer relative to that when water was used as an enhancer, and from 9 to 34 fold relative to that when ethanol was used as an enhancer. Also discussed are the possible mechanisms of action by which ethyl acetate increases the percutaneous absorption of drugs and use of ethyl acetate in transdermal drug delivery systems.