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Non-invasive analysis of penetration and storage of Isoconazole nitrate in the stratum corneum and the hair follicles

Isoconazole nitrate concentration in stratum corneum and hair follicle. Mean Isoconazole nitrate concentration (μmol) in stratum corneum (S.c.) and the pilosebaceous unit (PSU) up to 2weeks post last application of Travocort® cream on the forearm of nine evaluable volunteers. (MIC: minimum inhibitio...

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Published in:European journal of pharmaceutics and biopharmaceutics 2012-04, Vol.80 (3), p.615-620
Main Authors: Lademann, J., Patzelt, A., Schanzer, S., Richter, H., Thiede, G., Havlickova, B., Günther, C., Friedrich, M., Sterry, W., Fluhr, J.W., Seifert, S.
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Language:English
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Summary:Isoconazole nitrate concentration in stratum corneum and hair follicle. Mean Isoconazole nitrate concentration (μmol) in stratum corneum (S.c.) and the pilosebaceous unit (PSU) up to 2weeks post last application of Travocort® cream on the forearm of nine evaluable volunteers. (MIC: minimum inhibition concentration for growth inhibition of bacteria and fungi (according to Kessler et al. [18]); mean (S.c.): n=9 at day 0, n=7 at day 7, n=3 at day 14; mean (PSU): n=9 at day 0, n=8 at day 7.) Bacteria and fungi are located in the stratum corneum and the hair follicles. Therefore, the development and assessment of efficient drugs requires standard in vivo investigation methods permitting a differentiation between intercellular and follicular penetration and storage of topically applied anti-microbial substances. In the present study, the penetration and storage of Isoconazole nitrate in the stratum corneum and hair follicles was investigated by differential stripping after a 14-day topical application period and during a follow-up period of a further 21days. One week after the application had terminated, Isoconazole nitrate could still be detected in concentrations above the minimal inhibition concentration in the stratum corneum and the hair follicles. In some subjects, Isoconazole nitrate could even be detected 14days after the last application. No relevant changes in TEWL values were measured, indicating that the investigated compound did not induce an impairment of the barrier function. The study showed that differential stripping is suited to investigate the penetration and storage of topically applied substances into the stratum corneum and the hair follicles. Also, the hair follicles are a long-term reservoir for topically applied substances. This is of clinical importance, where a long-lasting therapeutic effect beyond the application time is required.
ISSN:0939-6411
1873-3441
DOI:10.1016/j.ejpb.2011.12.013