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

• Published in: European journal of pharmaceutical sciences 2007-12, Vol.32 (4), p.254-260
• Main Authors: Gunt, Hemali B., Kasting, Gerald B.
• Format: Article
• Language: English
• Subjects: Antifungal; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Biological and medical sciences; Diffusion; Drug delivery; General pharmacology; Humans; Humidity; Hydration; Ketoconazole - chemistry; Ketoconazole - pharmacology; Medical sciences; Nail; Nails - drug effects; Onychomycosis; Permeability - drug effects; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Time Factors; Tritium - chemistry; Water - chemistry
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2007.07.009

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 [ 3H]ketoconazole solvent-deposited onto the dorsal surface were maintained in incubators at 32 °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 [ 3H]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.