ENHANCEMENT EFFECTS IN THE PERMEATION OF ALPRAZOLAM THROUGH HAIRLESS MOUSE SKIN

Alprazolam (ALP) is an anxiolytic, antidepressant agent, having suitable features for the development of a transdermal medication. The objectives of this preliminary study were to determine: (a) whether ALP is absorbed in vitro through hairless mouse skin; (b) whether it is metabolized during diffusion, and (c) the influence of some chemicals on ALP penetration through skin. ALP permeates through hairless mouse skin in vitro. No degradation product of the drug resulted during skin permeation experiments, therefore, ALP was assumed to diffuse unchanged across the skin. Oleic acid (OLA), linoleic acid (LNA), linoleic acid diethanolamide (LNDA), coconut fatty acid diethanolamide (CNDA), lauric acid diethanolamide (LRDA), bis(2-hydroxyethyl)cocamine (HECA) and isopropyl lanolate (IPL) were evaluated with respect to their skin-permeation enhancing effect either as neat solvents or combined with propylene glycol (PG). All the vehicles excepting IPL and PG were more effective than OLA in enhancing transdermal absorption of ALP. The most effective was HECA followed by LNDA, CNDA and LNA/PG (8.5:1.5, w/w). The effects of skin pretreatment with HECA, LNA, LNDA and CNDA on the percutaneous absorption of ALP from a drug suspension in IPL were also investigated. For all the pretreatment vehicles ALP flux from IPL through pretreated skin was greater than that from IPL or OLA through untreated skin. In order to facilitate the interpretation of the absorption results, the stratum corneum/water, whole skin/water and n-octanol/water partition coefficients of the drug were determined.