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Enhancing, Measuring Skin Penetration
Posted: March 27, 2007
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Laser ablation of 12.6% of the surface area of stratum corneum produced a 2.8 and 2.1-times increase in permeability constant (kp) for 3H-hydrocortisone and 125I-gamma- interferon, respectively. These studies reportedly demonstrate that a pulsed mid-infrared laser can reliably and precisely remove the stratum corneum, facilitating penetration of large molecules such as 125I-gamma-interferon that cannot penetrate intact skin. This new technique could be useful for basic and clinical investigation of skin barrier properties. For more information, log on to: http://omlc.ogi.edu/.
The Wright State University Boonshoft School of Medicine reports on ways to study skin penetration--both in vitro and in vivo.
In vitro: One of the easiest ways to estimate penetration of drugs or chemicals through the skin is reportedly to take excised human (frequently leftover from surgeries) or laboratory animal (rat, guinea pig or pig) skin and place it between two chambers with the compound of interest in the donor chamber. In such in vitro studies, steady-state flux is determined by measuring the appearance of the compound in the receptor solution in the other chamber. Radioactive compounds are often used to make analysis of the receptor solution easier.
Steady-state flux (mass/time or mass/area/time) is determined from the slope of the linear portion of the cumulative chemical absorbed vs. time plot. Comparing these fluxes across a range of pharmaceutical products with exactly the same method allows acceptable rank-ordering of compounds for their ability to penetrate skin, which can be useful for selection of compounds or development of formulations. Unfortunately, this type of study reportedly does not provide information that is accurate enough for predicting the rate of penetration of a specific chemical in humans for a variety of reasons. Briefly, this is because of the dissimilarity between the environment of the skin in the diffusion cell and the skin on the human body (flux does not extrapolate very well). That said, careful experimentation with diffusion cells can provide fluxes that are “in the ballpark” and the studies are said to be cheaper and easier than whole animal pharmacokinetic studies.
In vivo: Studies of skin penetration in the whole animal have the potential to provide much better information because blood flow, metabolism as well as nervous and hormonal responses of the skin are intact; however, claims the report, they are much more expensive and time consuming. In vivo studies require particularly careful control of the dose applied to the skin. The surface area exposed and the concentration (or mass) on the skin are the driving forces for penetration and unlike diffusion cell studies where the area is carefully controlled and excess chemical is usually applied, these are harder to control in whole animal exposures.