Characterization of the permeability barrier of human skin in vivo

Abstract

Attenuated-total-ref lectance Fourier-transform-infrared spectroscopy has been used to rapidly and noninvasively quantify in vivo the uptake of a chemical into the outermost, and least permeable, layer of human skin (the stratum corneum). The objective of the experiment was to develop a general model to predict the rate and extent of chemical absorption for diverse exposure scenarios from simple, and safe, short-duration studies. Measurement of the concentration profile of the chemical in the stratum corneum, and analysis of the data using the unsteady-state diffusion equation, enabled estimation of the permeability coefficient and calculation of the time required to achieve maximal transdermal f lux. Validation of the spectroscopic technique employed was established, and quantitation of chemical uptake into the stratum corneum was confirmed independently using trace amounts of radiolabeled chemical in conjunction with liquid scintillation counting and accelerator mass spectrometry. The results presented have pharmacological and toxicological implications, as the technology lends itself both to the prediction of transdermal drug delivery, and the feasibility of this route of administration, and to the assessment of risk after dermal contact with toxic chemicals.The principal function of the skin is to act as a barrier to the insensible loss of tissue water. This objective is achieved by the stratum corneum (SC), the outermost layer of the epidermis, a lipid-protein biphasic structure, having a thickness of only 10 -20 m on most surfaces of the body. The excellent diffusional resistance of the SC makes the transdermal delivery of drugs at best difficult and frequently impossible. On the other hand, the SC protects against the dermal exposure of the organism to toxic chemicals. Nevertheless, there remains an important pharmaceutical need to reliably predict the topical and/or transdermal bioavailability of cutaneously applied drugs, and there is a crucial regulatory requirement for the accurate estimation of risk when inadvertent contact occurs between a potentially harmful substance and the skin.Because of the transport rate-limiting ability of the SC, it is reasonable to suppose that, from a chemical's concentration profile across the membrane, even after a relatively short exposure, all necessary information relating to permeability can be deduced. In this regard, previous research has involved application of radiolabeled chemicals followed by SC removal using repeated adhesive tape-stripping, and analysis of the tape-strips by liquid scintillation counting (1). If the dose is sufficiently large, on the other hand, and a suitable extraction procedure is available for the chemical, more conventional analytical tools (e.g., HPLC) can be used. While these approaches have been used in humans, neither is particularly satisfying because of the need to expose the subjects to a significant amount of radioactivity or to a possibly excessive quantity of the chemical itself.Recently, attenuated-total-reflectance F...

The determination of stratum corneum thickness An alternative approach

“…The first method considered was the linear model, LM, which has been widely used [1,8,[10][11][12][13]28] since its introduction [14,16]. The linear transformation of Fick's first law (Eq.…”

“…It was later withdrawn when the comparison of three products by two laboratories resulted in contradictory outcomes. Since then, some problems with the original guidance have been identified: (i) discarding two tape strips has lost favour, as drug in these outer layers would probably become available for absorption eventually [1,8] (ii) in an attempt to relate the drug concentration to a particular depth within the SC, and in order to normalise the data derived from different volunteers [1,[8][9][10][11][12], the total thickness of the SC is now measured [13,14].…”

Dermal uptake of chloroform and haloketones during bathing

“…Usually, the stratum corneum is modeled as a homogeneous membrane (Roy et al, 1996;Pirot et al, 1997). The passive diffusion of a chemical through the stratum corneum is represented by Fick's second law of diffusion as (Crank, 1975):…”

Transdermal Drug Delivery Systems: Skin Perturbation Devices

“…The SC, therefore is comprised of dead cells (corneocytes) interdispersed within a lipid rich matrix. It is the "brick and mortar" architecture and lipophilic nature of the SC, which primarily accounts for the barrier properties of the skin (1,2). The SC is also known to exhibit selective permeability and allows only relatively lipophilic compounds to diffuse into the lower layers.…”