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Evaluation of the effect of different fatty acids on the percutaneous absorption of metaproterenol sulfate.
Journal of Pharmaceutical Sciences 1996 January
The in vitro permeation rates of metaproterenol sulfate (MPS) across hairless mouse skin and TESTSKIN living skin equivalent were very low unless skin permeation enhancers were included in the vehicle. An optimum balance should be established between the chain length of the fatty acid and its molar ratio to MPS in order to enhance its penetration through the skin. Thus, the best flux values were shown by capric acid: MPS, 3:1 molar ratio, and lauric acid:MPS, 1:1 and 2:1 molar ratio, while myristic acid:MPS, 1:1 molar ratio, was the optimum under the experimental conditions used. The mechanism of the enhancing effect was examined by measuring 1H NMR spectra and the apparent partition coefficient of MPS, lauric acid, and the mixture. The apparent partition coefficient of MPS between n-octanol and water was higher for the mixture with lauric acid than for MPS alone. A 1:1 molar ratio formulation of MPS and lauric acid was selected for the in vivo permeation study. The data indicated that lauric acid increased the diffusivity of MPS in the skin by forming a complex and by affecting its partition coefficient between the skin and the delivery system.
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