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Monday 12 November 2007

Effect of hydration on the permeation of ketoconazole through human nail plate in vitro.

By: Gunt HB, Kasting GB.

Eur J Pharm Sci 2007 Dec;32(4-5):254-60

The impact of hydration on the permeation of the antifungal drug, ketoconazole, through excised human nails in vitro was evaluated in diffusion cell studies. Nails treated with [(3)H]ketoconazole solvent-deposited onto the dorsal surface were maintained in incubators at 32 degrees C and exposed sequentially to relative humidities (dorsal side) of 15, 40, 80 and 100% over a period of 40 days. The ventral side was bathed in a pH 7.4 phosphate buffer. Ascending and descending humidity regimens were tested. Increasing the ambient RH from 15 to 100% enhanced permeation of radiolabel associated with [(3)H]ketoconazole by a factor of three. Diffusivities estimated from these data and the associated nail water contents (estimated in a separate study) can be described by a free volume theory. Therefore, formulations or treatments, which increase nail hydration, have potential to improve topical therapy for onychomycosis, if a favorable balance between drug delivery and growth conditions for the dermatophytes can be achieved.

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