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• W2023187823 abstract "The effects of a series of fatty acids on the percutaneous absorption of propranolol (PL) through rabbit skin and the mechanism by which fatty acids facilitate the skin penetration of PL were examined in vitro and in vivo using a gel base. Lauric and myristic acids, at the fatty acid:PL molar ratio of 1:1 were the most potent agents in increasing the skin penetration, giving the largest penetration rate (Js and penetration coefficient (Kp) of PL. The molar ratio of 2:1 also exerted a large enhancing effect, comparable to that with a molar ratio of 1:1. When the enhancing effects of lauric acid, its amide, and its methyl ester were compared, the free acid gave the highest Js and Kp values. The plasma PL concentrations were significantly higher and more sustained after a single percutaneous application of the formulation with lauric acid than those after the formulation without the acid. The mechanism for the enhancing effect was examined by measuring IR and 13C NMR spectra, the solubility in buffer, and the apparent partition coefficient of PL. Additionally, the penetration of PL and lauric acid, as co-penetrants, through rabbit skin and shed snake skin were evaluated. The IR spectra of the mixture of PL with lauric acid (molar ratio, 1:1) was characterized by an extreme shift of the CO peak. Comparison of the NMR spectra of PL, lauric acid, and the mixture suggested that the carbonyl group of lauric acid interacted with the amino and hydroxyl groups of PL, probably by charge interaction. The apparent partition coefficient of PL between n-octanol and water was significantly higher for the mixture with lauric acid than for PL alone or the mixture with methyl laurate. Lauric acid and PL penetrated through snake skin, a model of the stratum corneum, at almost the same rate, while the penetration rate of lauric acid across whole rabbit skin was one-tenth that of PL. These results indicate that a significant portion of PL will penetrate across the stratum corneum by forming a complex with a fatty acid, and that the complex will dissociate to each component in the interface between the corneum and viable epidermis, where PL partitions into this water-rich tissue." @default.
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• W2023187823 date "1990-12-01" @default.
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• W2023187823 title "Mechanism for the Enhancement Effect of Fatty Acids on the Percutaneous Absorption of Propranolol" @default.
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• W2023187823 doi "https://doi.org/10.1002/jps.2600791206" @default.
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