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The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this study, hairless mouse dorsal skins were used as a modesl to select compsition of vehicle and AM. Basee on measurements of solubility and partition coefficient, the concentration of PG that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even whets the PG concentration was employed. To identify a suit-able absorption enhancer and its optimal concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (I.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped curve. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeatioN studies, and the extent was correlated with protein concentratior in the epidermal and serosal extract, and skin homogenates. In rat dorsal skins, the protein confentration decreased in the rank order of strain homogenate > serosal extracts > eqidermal extract. Estimated first order degradation rate constants were 6.15 +/- 0.14, 0.57 +/- 0.02 and 0.011 +/- 0.004 h-1 for skin homogenate,serosal extract and epidermal ectract, respectively. Therefore ,it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. Taken togethers our data indicated that transdermal delivey of AM is feasible when the combination of PG and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.
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