Combined effect of alcohol and urea on the in vitro transport of indomethacin across rat dorsal skin.

An aqueous gel, prepared with hydrogenated soya phospholipid, increased the in vitro transport of indomethacin across rat dorsal skin. The addition of various alkanols further accelerated the transport, with an increasing effect as the chain length of the alkanol increased. The addition of urea alone did not significantly affect the transport of indomethacin. However, the addition of urea markedly accelerated the transport of indomethacin when included in an aqueous gel containing an alkanol such as 1-octanol, 1-decanol, or 1-dodecanol. Thus, it appears that a combination of urea and these alkanols strongly enhances the transdermal absorption of indomethacin. Urea appears to accelerate enhanced drug transport into the stratum corneum by a mechanism involving the transport of urea enhanced by these alkanols.