RETENTION CAPACITY OF TOPICAL IMIDAZOLE ANTIFUNGAL AGENTS IN THE SKIN

studied the interaction between topical imidazole antifungal agents an d keratin, of which the main protein in the stratum corneum is compose d and which has a role ic determining the retention capacity of the ag ents in skin. In 50% (v/v) aqueous methanol solution, omoconazole (OMZ ) formed a precipitate in the presence of keratin. On Fourier-transfor m infrared (FTIR) spectroscopy of the precipitate, the peaks at about 1200-1500 cm(-1) changed in pattern and it was thus thought that OMZ b ound to keratin. In this case diffusion energy was measured and compar ed with other imidazole antifungal agents, bifonazole (BFZ) and clotri mazole (CTZ). The interaction energy obtained from the difference in d iffusion energy between the presence and absence of keratin was the hi ghest with OMZ (4.25 kcal/mol) and the lowest with BFZ (2.09 kcal/mol) . Retention capacity of OMZ in excised hairless mouse skin was 10.0 mu g/cm(2) at 24 h after application? whereas these values for BFZ and C TZ were 2.4 and 7.5 mu g/cm(2), respectively. These results suggested that the magnitude of interaction with keratin is an important factor in determining the retention capacity of imidazole antifungal agents i n skin. (C) 1998 Elsevier Science B.V.