Retention capacity of topical imidazole antifungal agents in the skin

studied the interaction between topical imidazole antifungal agents and keratin, of which the main protein in the stratum corneum is composed and which has a role ic determining the retention capacity of the agents in skin. In 50% (v/v) aqueous methanol solution, omoconazole (OMZ) formed a precipitate in the presence of keratin. On Fourier-transform infrared (FTIR) spectroscopy of the precipitate, the peaks at about 1200-1500 cm(-1) changed in pattern and it was thus thought that OMZ bound to keratin. In this case diffusion energy was measured and compared with other imidazole antifungal agents, bifonazole (BFZ) and clotrimazole (CTZ). The interaction energy obtained from the difference in diffusion energy between the presence and absence of keratin was the highest 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 CTZ 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 in skin. (C) 1998 Elsevier Science B.V.