Transdermal flux predictions for selected selective oestrogen receptor modulators (SERMs)

Comparison with experimental results

Sevgi Güngör, M. Begoña Delgado-Charro, Valérie Masini-Etévé, Russell O. Potts, Richard H. Guy

Research output: Contribution to journalArticle

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41 Downloads (Pure)

Abstract

The aim of this work was to evaluate the feasibility of delivering transdermally a series of highly lipophilic compounds (log P ~ 4-7), comprising several selective oestrogen receptor modulators and a modified testosterone (danazol). The maximum fluxes of the drugs were predicted theoretically using the modified Potts & Guy algorithm (to determine the permeability coefficient (kp) from water) and the calculated aqueous solubilities. The correction provided by Cleek & Bunge took into account the contribution of the viable epidermal barrier to the skin permeation of highly lipophilic compounds. Experimental measurements of drug fluxes from saturated hydroalcoholic solutions were determined in vitro through excised pig skin. Overall, the predicted fluxes were in good general agreement (within a factor of 10) with the experimental results. Most of the experimental fluxes were greater than those predicted theoretically suggesting that the 70:30 v/v ethanol-water vehicle employed may have had a modest skin penetration enhancement effect. This investigation shows that the transdermal fluxes of highly lipophilic compounds can be reasonably predicted from first principles provided that the viable epidermis, underlying the stratum corneum, is included as a potentially important contributor to the skin's overall barrier function. Furthermore, the absolute values of the measured fluxes, when considered in parallel with previous clinical studies, indicate that it might be feasible to topically deliver a therapeutically useful amount of some of the compounds considered to treat cancerous breast tissue.
Original languageEnglish
Pages (from-to)601-606
Number of pages6
JournalJournal of Controlled Release
Volume172
Issue number3
DOIs
Publication statusPublished - 28 Dec 2013

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Selective Estrogen Receptor Modulators
Skin
Danazol
Water
Epidermis
Pharmaceutical Preparations
Solubility
Cornea
Testosterone
Permeability
Breast
Ethanol
Swine

Cite this

Transdermal flux predictions for selected selective oestrogen receptor modulators (SERMs) : Comparison with experimental results. / Güngör, Sevgi; Delgado-Charro, M. Begoña; Masini-Etévé, Valérie; Potts, Russell O.; Guy, Richard H.

In: Journal of Controlled Release, Vol. 172, No. 3, 28.12.2013, p. 601-606.

Research output: Contribution to journalArticle

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