Effect of Several Penetration Enhancers on the Percutaneous Absorption of Indomethacin in Hairless Rats1)

Abstract

In order to measure the effect of several penetration enhancers on the percutaneous absorption of drugs and to classify the enhancers into several categories in terms of the mode and mechanism of action, in vitro permeation experiments with a model drug, indomethacin, from aqueous, ethanolic and binary solvent systems were carried out by using excised hairless rat abdominal skin and a 2-chamber diffusion cell at 37 °C. Among the enhancers used in the present experiments, Azone, dimethyl sulfoxide (DMSO), isopropylmyristate, diethylsebacate, diethylmethylbenzamide, methylpyrrolidone and salicyclic acid enhanced the skin permeation of indomethacin, whereas urea, pyrrolidonecarboxylic acid and sodium hyaluronate did not as compared with the same solvent system without enhancer. These results suggest that the lipophilicity of enhancers may be an important factor for the penetration-enhancing effect on the skin permeation of indomethacin. It is also suggested that the effect of methylpyrrolidone is dependent upon the kind of solvent system; higher water content resulted in a lower effect. Further experiments to clarify the mechanism of action were done with pyrrolidones and salicylates, since it has already been reported that other enhancers such as Azone and DMSO might mainly affect the lipid in skin. Pyrrolidones had an in vitro moisturizing effect on keratin tablets and an in vivo skin-moisturizing effect. They affected the dissolution of keratin powder. On the other hand, salicylates dissolved and softened keratin powder, but they had no effect on the skin moisturizing. These results suggest that pyrrolidones and salicylates affect the keratin cells in the stratum corneum to enhance skin permeability, although the mechanism of action is different between the two groups. © 1988, The Pharmaceutical Society of Japan. All rights reserved.