PERCUTANEOUS ABSORPTION 503 permeability of excised human skin to water after the surface lipid film has been removed with lipid solvents. Blank and Gould (121, 122) failed to discover any increased permeability of the skin in vitro to sodium dodecyl sulphate after removal of lipids from the cutaneous surface by washing with acetone, ethyl alcohol or an ethyl alcohol-ethyl ether mixture for a for a brief period. If this period of washing was extended to 3-4 days permeability to sodium dodecyl sulphate and to sodium laurate was greatly increased. These results show that organic solvents remove lipids only after prolonged contact with the skin. In the experiments mentioned above, lasting at most 24 h, it would seem unlikely that the increased per- meability observed is due to the removal of the skin lipid. The mechanism involved in the increase in permeability on removing the lipid in the stratum corneum by means of lipid solvents consists, according to Scheup- lein and Ross (146), of 'hole formation and loss ofwater-bindingcapacity'. In the case of'hydrogen-bonding solvents', for example DMSO and DMFA, the increased permeability is due to 'membrane expansion and uniform increase in media diffusivity' (146). Surface active agents Surface active agents differ considerably in their ability to penetrate the epidermal barrier, at least when low concentrations are employed. The penetration of sodium laurate and sodium dodecyl sulphate was investigated by Blank and Gould (94) on excised human abdominal skin. They found that 20 h after application, sodium laurate had penetrated the epidermis and dermis from weak (0.005 M) unbuffered, mildly alkaline aqueous solutions. Sodium dodecyl sulphate (0.005 M) on the other hand had penetrated only in very small quantities below the barrier and for the most part was retained in the stratum corneum. This difference was attributed to a greater affinity of the skin proteins to sodium dodecyl sulphate and is in keeping with the observations (147-149) that alkyl sulphates and alkyl benzene sulphonates combine with proteins to an appreciable extent. A difference between the in vivo rate of percutaneous absorption of n-dodecyl and n-hexadecyl sulphate in the rat was reported by Sprott (96). Using asS-labelled compounds in 0.65 mu concentration, the rate of excretion of ass in the urine after the application of n-hexadecyl asS- sulphate was twice that obtained following the application of n-dodecyl sulphate. Estimation of the amount of ass retained in the skin showed that the amount retained was inversely proportional to the amount absorbed.

504 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS According to Sprott (96) retention in the skin depends on the ability of the surfactant to interact with proteins the greater this interaction the greater the amount retained locally and the less passes through. At concentrations appreciably higher than those employed in the studies just mentioned, surfactants enhance percutaneous absorption. Studies by Sprott (96) indicated that surfactants promote the penetration of water and sodium iodide in vivo. Using tritiated water and mI sodium iodide he showed that pre-washing the shaved skin of rats with a bar of 'ordinary' soap increased the penetration rate three-fold. When the soap contained a high proportion of sulphonated fatty acids and fatty acid esters of isethionic acid, there was a four-fold increase in the rate of penetration. Similar in- creases in the rate of penetration of •a•iodide were observed after pretreat- ment of the skin with these two types of soap. A similar enhancement of percutaneous absorption following applica- tion of surfactants was obtained in an earlier study (150, 151) on the influence of alkylaryl-sulphonates and soap on the percutaneous absorption of mercuric chloride and methyl mercury dicyandiamide. Both compounds were labelled with •'øaHg. The mercury compounds were dissolved in water, and in a 1•o aqueous solution of soap and alkylaryl sulphonate, respec- tively. The presence of soap did not influence the absorption of the two mercury compounds. The presence of alkylaryl sulphonate increased the absorption of the organo-mercury compound and to a lesser extent that of mercuric chloride. These results confirmed other observations by these authors using the same mercury salts and surfactants (151). The addition of 0.2•o sodium lauryl sulphate or 1.0•o polysorbate 80 to solutions of chloramphenicol doubled the rate of penetration of this drug (98). Even at lower concentrations, surfactants enhance percutaneous absorption. Using a 0.50 nm concentration of the sodium salts of C8-C•8 straight chain fatty acids, Sprott (96) found that the rate of penetration of tritiated water was increased with C8-Cx4 fatty acid salts, the fatty acids with the shorter chain being the more effective. With a chain length of over C•4 no effect on percutaneous absorption was observed. The sodium salts of alkyl aryl sulphonates at the same concentrations also increased per- cutaneous absorption. In this instance the longer the chain length the more effective was the compound. Bettley (45) correlated the surface activity of a series of ionic surfactants in vitro at 0.04 m concentration with their effect on permeability. He found that the potassium salts of caprylic acid and lauric acid, which depress surface tension to an almost equal degree, differed widely in their ability to enhance the permeability of the stratum