BILE-ACIDS AS ENHANCERS OF STEROID PENETRATION THROUGH EXCISED HAIRLESS MOUSE SKIN

Excised hairless mouse skin (EHMS) is used to evaluate the potential of sodium choleate (NaCOL), an ox bile extract containing the sodium salts of taurocholic, glycocolic, desoxycholic and cholic acids, and of the free choleic acids (HCOL) to enhance the transcutaneous penetration of progesterone (PGT) and prednisolone (PDN). EHMS is pretreated with aqueous dispersions of the enhancers, then the steroids are allowed to permeate through the pretreated EHMS from normal saline under occluded conditions. NaCOL is ineffective whereas HCOL produces structural modifications of the stratum corneum, resulting in increased skin permeability of both steroids. The chloroform-soluble components of HCOL interact strongly with stratum corneum lipids, as demonstrated by differential scanning calorimetry, thus facilitating PGT penetration. The chloroform-insoluble components of HCOL interact with more polar structures of stratum corneum, thereby promoting PDN transport. The data also suggest the existence of a parallel drug co-transport mechanism by the more lipophilic HCOL components.