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Topical delivery of a naproxen-dithranol co-drug: in vitro skin penetration, permeation, and staining

Lau, W.-M., White, A. W. and Heard, C. M. (2010) Topical delivery of a naproxen-dithranol co-drug: in vitro skin penetration, permeation, and staining. Pharmaceutical Research, 27 (12). pp. 2734-2742. ISSN 0724-8741

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To link to this article DOI: 10.1007/s11095-010-0274-8

Abstract/Summary

Purpose This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. Method Freshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining. Results Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm-² and 180 ± 60 nmol cm-², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol. Conclusions Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
ID Code:7913
Uncontrolled Keywords:anti-proliferative; co-drug; ester; hydrolysis, prodrug, psoriasis
Publisher:Springer Verlag

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