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-dim ethylamino)propionate (II; DDAIP), was prepared by reacting dodecyl 2- bromopropionate (I), obtained by reaction of n-dodecanol with 2-bromop ropionyl halogenide, with dimethylamine. The penetration enhancing eff ects of DDAIP on the transport of indomethacin, clonidine, and hydroco rtisone across shed snake skin (Elaphe obsoleta) were evaluated. Azone and lauryl alcohol, a possible decomposition product of DDAIP, were u sed as standard enhancers for comparison. In terms of flux, DDAIP show ed 4.7 and 7.5 times the promoting effect for indomethacin compared to azone and lauryl alcohol, respectively. With clonidine this effect wa s 1.7 and 3.1 times, whereas with hydrocortisone it was 2.4 and 2.8 ti mes higher, respectively. In vitro biodegradability of DDAIP was demon strated in the presence of porcine esterase. The results indicate that DDAIP increases markedly the transepidermal delivery of several types of drug substances.