Effect of the aggregation state of bile salts on their transdermal absorption enhancing properties

Surfactants have been studied as transdermal enhancers since they are able to solubilize drugs into micelles and interact with constituents of the skin. However, and perhaps surprisingly, bile salts (BS) have been practically overlooked. This study investigated BS as transdermal enhancers, with emphasis on the role of their aggregation state on this property. Bile salts were cholate and deoxycholate since they represent opposite cases of lipophilicity among micelle-forming BS. Acetaminophen, trimetroprim, and metoprolol were chosen as model drugs. Drug permeability enhancement ratio (Papp) values were calculated, in absence and presence of BS, both below and above their critical micelle concentration, and permeability enhancement ratio (PER) was obtained. Control Papp ranged from 3.5–12.4 × 10−7 cm/s, being acetaminophen the most permeable drug. In general, micelles of BS exerted repressing effects on drug Papp, with PER values ranging from 0.08 to 0.89. On the other hand, the impact of monomeric BS on drug Papp, when present, were promoting with PER values ranging from 1.04 to 2.78, being deoxycholate a more effective transdermal promoter than cholate. In specific, deoxycholate monomers increased 2.2-fold the transdermal absorption of the low molecular weight drug acetaminophen. Monomeric BS behave as transdermal enhancers whose intrinsic effectiveness depends on their lipophilicity.