Permeability, skin

Dichlorvos Diethyl ether Diethyl phthalate Diethylene glycol 

Mercury compounds (organic and inorganic) Methacrylic acid 

Selenium compounds Sodium azide Sodium carbonate Sodium fluoride Sodium hydroxide Sodium hypochlorite Sodium metabisulfite Stoddard solvent 

Styrene Sulfuric acid Tetrachloroethylene Thallium compounds Tin compounds Toluene 

In the second study, carried out a quarter of a century earlier, it was reported that skin permeability was increased after treatment with nonpolar solvents, and that permeability constants for a homologous series of alcohols were a function of increasing carbon number. What the authors of that study did not report is that the increased permeability observed corresponds exactly to increasing Kqw values. The data in Table 27.2 show the relationship between permeability constants (K and 

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Humidity and temperature also affect permeability. It has long been known that skin hydration, however brought about, increases skin permeability. Occlusive... 

Temperature influences skin permeability in both physical and physiological ways. For instance, activation energies for diffusion of small nonelectrolytes across the stratum corneum have been shown to lie between 8 and 15 kcal/mole [4,32]. Thus thermal activation alone can double the rate skin permeability when there is a 10°C change in the surface temperature of the skin [33], Additionally, blood perfusion through the skin in terms of amount and closeness of approach to the skin s surface is regulated by its temperature and also by an individual s need to maintain the body s 37° C isothermal state. Since clearance of percuta-neously absorbed drug to the systemic circulation is sensitive to blood flow, a fluctuation in blood flow might be expected to alter the uptake of chemicals. No clear-cut evidence exists that this is so, however, which seems to teach us that even the reduced blood flow of chilled skin is adequate to efficiently clear compounds from the underside of the epidermis. 

While the model helps us understand the chemical structure dependencies of skin permeability, it isn t all that useful for calculating permeability coefficients because of the many iffy assumptions it contains. A different tack has to be taken to gain a sense of the limits, especially the upper limit, of cutaneous drug delivery. There is no lower limit. Even proteins penetrate intact skin to some extent. Some idea of the upper... 

Crystallinity aside, the two physical attributes of a drug that most control its skin permeability are its physical size and its lipophilicity [44,45]. When all extant human permeability coefficients (at the time over 90 compounds) were subjected to multiple linear regression by Potts and Guy using the following semi-empirical equation [45] ... 

Abraham, M. H. Martins, F. Mitchell, R. C., Algorithms for skin permeability using hydrogen bond descriptors The problems of steroids, J. Pharm. Pharmacol. 49, 858-865 (1997). 

Hydration can be an important factor in diffusion and mass transport phenomena in pharmaceutical systems. It may alter the apparent solubility or dissolution rate of the drug, the hydrodynamic radii of permeants, the physicochemical state of the polymeric membrane through which the permeant is moving, or the skin permeability characteristics in transdermal applications. 

Kahns, A. H., Moss, J., Bundgaard, H., Human skin permeability studies... 

The effect of pH on skin permeability, accumulation, and penetration was studied for some important drugs such as insulin for glucose control [175], acyclovir for HIV-related conditions [176] and 5-fluorouracil for cancer treatment [177],... 

Most chemicals are not absorbed readily by the skin. A few chemicals, however, do show remarkable skin permeability. Phenol, for example, requires only a small area of skin for the body to absorb an adequate amount to result in death. 

As described previously in this chapter, efforts have been made to develop methods for quantification of skin permeability, validation of diffusion cell setups, and correlation of in vitro data with the in vivo situation. However, the average drug permeation experiment does not provide insight into the temporal and local disposition within the tissue, that is, the skin penetration. The following discussion will give an overview of methods tackling this kind of problem. 

Y. Yamaguchi, T. Usami, H. Natsume, T. Aoyagi, Y. Nagase, K. Sugibayashi, and Y. Morimoto. Evaluation of skin permeability of drugs by newly prepared polymer membranes. Chem. Pharm. Bull. 45 537-541 (1997). 

T. Hatanaka, M. Inuma, K. Sugibayashi, and Y. Morimoto. Prediction of skin permeability of drugs. II. Development of composite membrane as a skin alternative. Int. J. Pharm. 79 21-28 (1992). 

Keywords Skin permeability Percutaneous absorption Skin penetration Mathematical model Quantitative structure-activity relationships Permeability coefficient Human skin... 

Starting from Eq. 12 several similar models were developed for predicting skin permeability. Probably the most popular such model was presented by Potts and Guy in 1992 [19], Instead of using Eq. 8, Potts and Guy estimated the diffusion coefficient in human skin using the relationship... 

In 2003, Mitragotri developed a model for predicting stratum corneum permeability which included four different pathways. The overall skin permeability was described by the following equation ... 

Many QSPR models rely on some sort of idealized theoretical model for the transport of a molecule through the skin barrier. The descriptors necessary for predicting skin permeability—usually molecular weight and the octanol-water... 

The properties of a formulation and its composition affect skin permeability. For example, the pH of formulations was shown to have an effect on skin permeability. Using experimental data a predictive model could be established [86], A mechanistic understanding of this effect is still missing—as well as a purely computational model. Various substances are known to enhance... 

Kirchner LA, Moody RP, Doyle E, Bose B, Jeffry J, Chu I (1997) The prediction of skin permeability by using physicochemical data. ATLA 25 359-370. 

Frasch HF, Landsittel DP (2002) Regarding the sources of data analyzed with quantitative structure-skin permeability relationship methods. Eur J Pharm Sci 15 399-403. 

Pugh WJ, Hadgraft J (1994) Ab initio prediction of human skin permeability coefficients. Int J Pharm 103 163-178. 

Abraham MH, Martins F (2004) Human skin permeability and partition general linear free-energy relationship analysis. J Pharm Sci 93 1508-1523. 

Mitragotri S (2003) Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways. J Contr Rel 86 69-92. 

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