Drug Permeation Through Human Skin II: Permeability of Ionizable Compounds

Swarbrick, James; Lee, Geoffrey; Brom, Jeffrey; Gensmantel, Nigel P.

doi:10.1002/jps.2600731006

Cited by 84 publications

(31 citation statements)

References 13 publications

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“…Table 3 lated from six individual experiments on stratum corneum excised from the upper thigh of a single cadaver. The mean value of 3.97 x 10 -12 _ 2.33 X 10 12 cm 2 S-1 is reasonable for drug molecules of this structure and size (Swarbrick et al, 1984). The standard deviation compares very favourably with literature data.…”

Section: Resultssupporting

confidence: 70%

Measurement of drug diffusivity in stratum corneum membranes and a polyacrylate matrix

Göpferich¹,

Lee²

1991

International Journal of Pharmaceutics

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Summa~Diffusivities have been determined for the drug clenbuterol for three non-sink, diffusional problems: diffusion out of a polymer matrix, diffusion through excised, human stratum corneum, and the combined case of diffusion out of a polymer matrix through contiguous, excised stratum corneum. Numerical solution of the diffusion equation for these problems yields theoretical values of drug mass in the acceptor phase, ma(t)th, VS time. Diffusion was then measured experimentally and the best value for diffusivity obtained by comparing the values of drug mass in the acceptor phase, ma(t)exp, with the corresponding ma(t)t h data. In this fashion it was possible to obtain diffusivities for diffusion out of the polymer matrix for various values of drug loading and matrix thickness. For the problem of diffusion through stratum corneum a value for the partition coefficient of clenbuterol as well as for its diffusivity could be determined. The two diffusivities obtained for the combined model (i.e., D m within the matrix and D s within the stratum corneum) agree quite well with those obtained for the two separate problems, but are more scattered. Partition coefficients could not be accurately determined for diffusion out of the matrix or the combined problem.

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Section: Resultssupporting

confidence: 70%

Measurement of drug diffusivity in stratum corneum membranes and a polyacrylate matrix

Göpferich¹,

Lee²

1991

International Journal of Pharmaceutics

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“…5) The findings were also consistent with those on 4-oxo-4H-1-benzopyran-2-carboxylic acids in human skin, 11) although the relative contribution of ionic permeation was smaller than that observed in this study.…”

supporting

confidence: 89%

“…4,5,11) Although the value for the ionized form was much smaller than that for the nonionized form, ionic permeation does not seem to be negligible at weakly acidic skin pHs. These findings are consistent with previous findings on diclofenac by Obata et al in hairless rats, 4) and on indomethacin in hairless rats.…”

mentioning

confidence: 94%

Permeability of Ionized Salicylate Derivatives through Guinea Pig Dorsal Skin

Kamal

Nabekura

Kitagawa

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…There is also good evidence that the SC is much more permeable to neutral molecules than to ions of weak acids or bases. 20,21) The non-ionic form of resveratrol shows high lipophilicity according to the partition coefficient (log P octanol/water ϭ3.32). The partition coefficient for compounds between SC and water (log P SC/water ) can be estimated as 22) : log P SC/water ϭϪ0.024ϩ0.59 log P octanol/water .…”

Section: Discussionmentioning

confidence: 99%

Delivery of Resveratrol, a Red Wine Polyphenol, from Solutions and Hydrogels <i>via</i> the Skin

Hung

Lin

Huang

et al. 2008

Biological & Pharmaceutical Bulletin

105

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Resveratrol is a naturally occurring polyphenolic compound which has received much attention in the prevention of and therapy for cardiovascular diseases and cancers ( Fig. 1).1) Red grapes and wines contain considerable amounts of resveratrol. Resveratrol has many benefits for the skin. Topically applied resveratrol has been shown to possess strong antiproliferative and chemopreventive properties against skin carcinogenesis.2-4) Resveratrol affords substantial protection against skin damage from ultraviolet B (UVB) exposure. 5,6) Resveratrol shows antimicrobial activity against dermatophytes and herpes simplex virus. 7,8) Resveratrol can also be used in the dermocosmetic field because of its role as a phytoestrogen based on its ability to activate estrogen receptors. 9)The oral bioavailability of resveratrol is poor, leading to an irrelevant in vivo effect with oral administration compared to its powerful in vitro efficacy. 10) Resveratrol also has a short initial half-life (8-14 min) and is extensively metabolized in the body.11) Several phase I clinical trials are currently underway for oral resveratrol in humans at doses of as high as 7.5 g per day. This would require 2.7 kg of resveratrol a year at a current cost of ca. US$6800. Therefore it is becoming increasingly important to find ways to improve the bioavailability of and block the metabolism of resveratrol. Delivery of resveratrol via the skin is an attractive alternative to oral dosing for both topical and transdermal applications.No evidence currently exists in the literature to support the notion that a sufficient amount of resveratrol can be delivered to produce therapeutic benefits via a skin route. Designs of optimal formulations for resveratrol permeation via the skin are also lacking. The purposes of this study were to establish basic profiles of resveratrol permeability into and across the skin. The optimal pH and co-solvent of the vehicles for resveratrol were investigated for better permeation. The present study utilized Franz cells to explore the in vitro skin permeation of resveratrol. The drug amount retained within the skin reservoir was determined by in vitro and in vivo methods. Various skin membranes, including nude mouse skin, stratum corneum (SC)-stripped skin, delipidized skin, and cellulose membranes, were used as permeation barriers to elucidate the mechanisms and pathways. One particular problem common to drug delivery systems designed for use on the skin is the poor retention at the site of application. This problem can be resolved by incorporating bioadhesive hydrogels within the system. Hence, the ability of a series of hydrogel formulations to deliver topically applied resveratrol was examined. The permeability of piceatannol (Fig. 1), a resveratrol analogue with considerably higher activity, was also evaluated in this study. Resveratrol, the main active polyphenol in red wine, has been demonstrated to show benefits against skin disorders. The bioavailability of orally administered resveratrol is insufficient to permit high...

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Drug Permeation Through Human Skin II: Permeability of Ionizable Compounds

Cited by 84 publications

References 13 publications

Measurement of drug diffusivity in stratum corneum membranes and a polyacrylate matrix

Measurement of drug diffusivity in stratum corneum membranes and a polyacrylate matrix

Permeability of Ionized Salicylate Derivatives through Guinea Pig Dorsal Skin

Delivery of Resveratrol, a Red Wine Polyphenol, from Solutions and Hydrogels <i>via</i> the Skin

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