ENHANCED DELIVERY OF 5-FLUOROURACIL THROUGH SHED SNAKE SKIN BY 2 NEW TRANSDERMAL PENETRATION ENHANCERS

The effectiveness of a new biodegradable penetration enhancer, dodecyl N,N-dimethylamino isopropionate (DDAIP) was compared to dodecyl N,N-d imethylamino acetate (DDAA), another biodegradable penetration enhance r, and to Azone(R), lauryl alcohol (LA), and oleic acid (OA) in vitro using shed snake skin in modified Franz-type diffusion cells. 5-Fluoro uracil (5FU), a hydrophilic drug with poor skin permeability, was used as a model permeant. Skin samples were pretreated with pure liquid en hancers. 5FU flux through the control and enhancer treated skin increa sed linearly with its concentration in the donor compartment. DDAIP an d DDAA interacted with the skin rapidly (< 2 h), and the duration of a ction is at least 24 h. The transdermal flux of 5FU increased substant ially (> 40-fold) with the dose of DDAIP up to 10 mul. Thereafter the flux did not increase significantly. With DDAA no plateau effect was o bserved with the applied volumes up to 50 mul. Skin pretreatment with 5 mul of DDAIP, DDAA, Azone(R), LA, and OA increased the permeability of 5FU 69-, 24-, 23-, 5-, and 2-times, respectively. Substitution of a methyl group for a hydrogen atom in the acetate moiety of DDAA was ob served to markedly increase transdermal penetration enhancement.