Synthesis and enhancing effect of dodecyl 2-(N,N-dimethylamino)propionate on the transepidermal delivery of indomethacin, clonidine, and hydrocortisone

The biodegradable transdermal penetration enhancer, dodecyl 2-(N,N-dimethylamino)propionate (II; DDAIP), was prepared by reacting dodecyl 2-bromopropionate (I), obtained by reaction of n-dodecanol with 2-bromopropionyl halogenide, with dimethylamine. The penetration enhancing effects of DDAIP on the transport of indomethacin, clonidine, and hydrocortisone across shed snake skin (Elaphe obsoleta) were evaluated. Azone and lauryl alcohol, a possible decomposition product of DDAIP, were used as standard enhancers for comparison. In terms of flux, DDAIP showed 4.7 and 7.5 times the promoting effect for indomethacin compared to azone and lauryl alcohol, respectively. With clonidine this effect was 1.7 and 3.1 times, whereas with hydrocortisone it was 2.4 and 2.8 times higher, respectively. In vitro biodegradability of DDAIP was demonstrated in the presence of porcine esterase. The results indicate that DDAIP increases markedly the transepidermal delivery of several types of drug substances.