The purpose of this study was to investigate the feasibility of transdermal drug delivery of ondansetron, an antagonist of the 5-HT3 receptor, used for the treatment of chemotherapy-induced emesis. The permeability of ondansetron from an aqueous suspension through shed snake skin as a model membrane was very low and in order to improve it, several enhancers were tested. Ethanol increased the flux at a concentration of 40% or more. The solubility of ondansetron also increased as the ethanol concentration increased. The permeability coefficient increased after pretreatment of the shed snake skin with Azone, oleic acid or lauryl alcohol. Further improvement of the permeability was observed when ethanol was combined with other enhancers and was maximum for the combination of ethanol and oleic acid. Oleic acid dramatically increased the partition of ondansetron to n-hexane and shed snake skin. Oleic acid may enhance the permeation of ondansetron in two ways: by a direct effect on the stratum corneum or via counterion formation of an ion-pair. The maximum flux obtained from the combination of ethanol and other enhancers seems to be high enough to obtain a therapeutic effect.
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