Mechanistic study into the enhanced transdermal permeation of a model beta-blocker, propranolol, by fatty acids: a melting point depression effect.

Transdermal permeation of propranolol through human skin in the presence of fatty acid (lauric, capric) penetration enhancers has been investigated. Thermal analysis showed that binary mixtures of propranolol with either fatty acid were not simple mechanical mixtures of the two components. Propranolol formed 1:1 molar addition compounds with both lauric and capric acids; the addition compound produced from propranolol and lauric acid (m.p. 79 degrees C) also developed eutectic systems with both propranolol (m.p. 54 degrees C) and lauric acid (m.p. 16 degrees C). Similarly, the addition compound made from propranolol and capric acid (m.p. 97 degrees C) formed eutectic systems with propranolol (m.p. 83 degrees C) and capric acid (m.p. 15 degrees C). Infrared analyses indicated that the addition compounds were fatty acid salts of the beta-blocker. The nature of the species permeating through human epidermal membranes from binary mixtures of propranolol with the fatty acids was investigated using a novel attenuated total reflectance Fourier transform infrared method. There was no clear difference in permeation rates of the fatty acids compared with the beta-blocker, suggesting that the permeating species was the intact addition compound. The influence of melting point depression of the beta-blocker fatty acid systems on transdermal permeation was predicted from a mathematical model; predicted and experimentally determined data correlated well thus providing an alternative explanation as to the mode of action of these permeation enhancers.