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Pharmaceutical Research

, Volume 27, Issue 12, pp 2734–2742 | Cite as

Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining

  • Wing Man LauEmail author
  • Alex W White
  • Charles M Heard
Research Paper

ABSTRACT

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.

KEY WORDS

anti-proliferative co-drug ester hydrolysis prodrug psoriasis 

ABBREVIATIONS

HMPA

Hexamethylphosphoramide

IPM

Isopropyl myristate

LOD

limit of detection

MW

molecular weight

Nap-DTH

Naproxyl-dithranol

SC

stratum corneum

THF

Tetrahydrofuran

Notes

ACKNOWLEDGEMENTS

The authors would like to acknowledge the financial support from Stiefel Laboratories, UK.

Conflict of interest

None declared.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Wing Man Lau
    • 1
    • 2
    Email author
  • Alex W White
    • 1
  • Charles M Heard
    • 1
  1. 1.Welsh School of PharmacyCardiff UniversityCardiffUK
  2. 2.School of PharmacyUniversity of ReadingReadingUK

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