Permeation of Mouse Skin and Silicone Rubber Membranes by Phenols: Relationship to In Vitro Partitioning

Jetzer, W.; Huq, Abu S.; Ho, Norman F.H.; Flynn, Gordon L.; Duraiswamy, Nandini; Condie, Lyman W.

doi:10.1002/jps.2600751116

Cited by 31 publications

(17 citation statements)

References 11 publications

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“…3C) is similar to the slope of 0.7 reported by Potts and Guy (21). A linear relationship between log k p and log P has also been reported for mouse skin and silicone rubber membranes (66). Further, in the present study, the hydrogen bonding properties of the solutes did not appear to be significant determinants for J max .…”

Section: Discussionsupporting

confidence: 89%

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Zhang

Grice

et al. 2009

Pharm Res

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A key finding is that the convex dependence of maximum flux on lipophilicity arises primarily from variations in stratum corneum solubility, and not from diffusional or partitioning barrier effects at the stratum corneum-viable epidermis interface for the more lipophilic phenols. Our data support a solute structure-skin transport model for aqueous solutions in which permeation rates depend on both partitioning and diffusivity: partitioning is related to P, and diffusivity to solute size and hydrogen bonding.

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Section: Discussionsupporting

confidence: 89%

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Zhang

Grice

et al. 2009

Pharm Res

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“…This concentration-related increase in diffusivity has been attributed to polymer plasticisation arising from an increase in polymer-free volume with the higher uptake of solute/solvent at higher concentrations [52]. Interestingly, a similar concentration-dependent increase in phenol flux also appears to occur [12,26,27]. However, we have shown that this increase is also associated with changes in the stratum corneum morphology.…”

Section: Irvin Blank - the Precise Defining Of Solute Structure-skin mentioning

confidence: 50%

“…The importance of equations 2 and 4 is that both give a means to reconcile percutaneous penetration and toxicity for solutes from different vehicles. Thus, as Higuchi points out and as I learned during my PhD, at equal concentrations, phenol is bland to the skin when applied in glycerol, dimethyl sulfoxide or propylene glycol in which it is exceedingly soluble but quite corrosive in water above 2% for both human [12] and mouse skin [26,27]. Gordon Flynn [pers.…”

Section: Takeru Higuchi - Defining the Theoretical Principles Underpimentioning

confidence: 99%

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

Roberts¹

2013

Skin Pharmacol Physiol

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An appreciation of solute-vehicle-skin interactions underpins our current understanding of the processes of percutaneous absorption as well as in the prediction of the extent of absorption. This understanding has been reached through principles developed and validated over the last century through the work of a number of authors, including Dale Wurster, Takeru Higuchi, Irvin Blank, Robert Scheuplein, Gordon Flynn, Boyd Poulsen and Tom Franz, as well as by many scientists from my and younger generations. Their work has led to an appreciation of the rate-limiting steps in percutaneous penetration, the role played by the physicochemical properties of the solute, vehicle and skin and the variability that may arise from using various experimental/mathematical/pharmacokinetic models to quantify absorption as well as enabling the prediction of local and systemic efficacy and toxicity. In addition, unexpected behaviour may result from non-ideality in solute-vehicle-skin effects, including dehydration, chemical enhancement, supersaturation, metabolism, sequestration and vascular effects, including those of nanosystems on the local vasculature. In general, in vitro skin penetration profiles are predictive of in vivo profiles but a number of exceptions also exist.

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“…12) To examine the possibility of the involvement of the ion-pair formation between salicylate and the cationic surfactants such as 2C10, we next examined the effects of ndimethyldialkylammoniums on the permeation of silicon rubber membrane; Since permeation of drugs through silicon rubber membrane follows the pH-partition hypothethis, 13) and the membrane has been used to study the possibility of the contribution of the ion-pair formation on the enhancement effects of various skin permeation enhancers. 14) Undissociated forms of salicylic acid rapidly permeated through the silicon rubber membrane, which was shown as a large permeability coefficient value at acidic pH (pH 2.6) in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Enhancement Effects of Double-Chained Cationic Surfactants of n-Dimethyldialkylammoniums on Permeability of Salicylate through Guinea Pig Dorsal Skin.

Kitagawa

Kasamaki

2002

Chem. Pharm. Bull.

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It has been demonstrated that various kinds of surfactants disrupt the barrier function of skin and increase transdermal drug permeability.1) Among them, long-chain cationic surfactants such as n-dodecyltrimethylammonium (1C12) are known to have marked enhancement effects on the transdermal permeation of hydrophilic drugs.2,3) These cationic surfactants seem to interact with proteins in the stratum corneum as well as the lipid lamella, improve the hydrophilic property of the skin and enhance the skin permeation of relatively hydrophilic drugs. 3)Different from the single-chained cationic surfactants, some of the double-chained cationic surfactants form bilayer vesicles just like phospholipids. [4][5][6] We recently examined the effects of double-chained cationic surfactants of n-dimethyldialkylammoniums (CH 3 ) 2 N ϩ (C n H 2nϩ1 ) 2 on skin permeation of undissociated form of benzoic acid through excised guinea pig dorsal skin at acidic donor pH conditions. 6)n-Dimethyldialkylammoniums with relatively shorter alkyl chains such as dimethyldidecylammonium (2C10) seem to form micelles instead of vesicles. The findings on the five double-chained cationic surfactants tested (nϭ10-18) revealed the marked enhancement effects of the surfactants with relatively shorter alkyl chains, whose enhancement mechanism is possibly similar to that of single-chained cationic surfactants.The enhancement effects of the cationic surfactants may be different depending on the electric charge of the drugs. Therefore, in this study we examined the effects of five n-dimethyl-and n-dimethyldistearylammonium (2C18) on in vitro skin permeation of anionic drugs using salicylate, whose pK a value is 3.0, 7) as a model drug. We compared their enhancement effects with those on undissociated forms of drugs we previously reported.6) We also compared their enhancement effects on the permeation of salicylate with those of singlechained cationic surfactants of n-alkyltrimethylammoniums and those of the vesicles consisting of n-dimethyldialkylammoniums and egg yolk phosphatidylcholine (egg yolk PC). In order to clarify the mechanism of the enhancement, we furthermore examined the effects of n-dimethyldialkylammoniums on the permeation of salicylate though silicon rubber membrane. We also examined their effects on the skin content of salicylate.Experimental Materials Bromide salts of n-dimethyldialkylammoniums and nalkyltrimethylammoniums were purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Sodium salicylate, egg yolk phosphatidylcholine (egg yolk PC) and all other reagents were from Wako Pure Chemical Industries. Silicon rubber sheet was purchased from GE Toshiba Silicones Co., Ltd. (Ota, Japan).Preparation of Surfactant Solutions and Sonicated Dispersions nDimethyldialkylammoniums were used after preparing the sonicated dispersions as described previously.6) Bromide salts of n-dimethyldialkylammoniums were dissolved in chloroform, and the solvent was evaporated. Dried surfactant films were prepared by removing the solvent under vacuum...

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Permeation of Mouse Skin and Silicone Rubber Membranes by Phenols: Relationship to In Vitro Partitioning

Cited by 31 publications

References 11 publications

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Skin Solubility Determines Maximum Transepidermal Flux for Similar Size Molecules

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

Enhancement Effects of Double-Chained Cationic Surfactants of n-Dimethyldialkylammoniums on Permeability of Salicylate through Guinea Pig Dorsal Skin.

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