Article

Assessment of drug permeability distribution in two different model skins

University of Strathclyde, Glasgow, Scotland, United Kingdom
International Journal of Pharmaceutics (Impact Factor: 3.65). 11/2005; 303(1-2):81-7. DOI: 10.1016/j.ijpharm.2005.07.005
Source: PubMed

ABSTRACT Past in vitro studies with human skin have indicated that drug permeability coefficient (Kp) distributions do not always follow a Gaussian-normal pattern. This has major statistical implications, exemplified by the fact that use of t-tests to evaluate significance is limited to normally distributed populations. Percutaneous absorption research often involves using animal or synthetic skins to simulate less readily available human skin. However, negligible work has been performed on assessing the permeability variabilities of these model membranes. This paper aims to fill this gap. To this end, four studies were undertaken representing two different drugs (caffeine and testosterone) with each drug penetrating through two different model skins (silicone membrane and pig skin). It was determined that in the silicone membrane studies, both compounds' Kp distributions could be fitted to a normal pattern. In contrast, in the pig skin studies, there were notable differences between each drug. While the testosterone Kp values could be fitted to a normal distribution, this was not possible with the caffeine Kp data, which could be fitted to a log-normal distribution. There is some evidence from the literature as well as physicochemical considerations that these outcomes may reflect general trends that are dependent upon both membrane and penetrant properties.

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Available from: Gul Majid Khan, Aug 26, 2015
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    • "Often models are based on parameters such as the lipophilicity and molecular weight (or size) of a drug (Magnusson et al., 2004; Ng et al., 2012; Potts and Guy, 1992; Singh and Roberts, 1996), although other, related physicochemical parameters have been investigated in an attempt to improve the predictivity of the models . Another approach employed to predict the ability of a drug to permeate the skin is to employ in vitro based model systems, for example those that have been successfully used to predict other biological permeations; such as those based on the blood–brain barrier (Sinkó et al., 2012), using electrokinetic chromatography (Wang et al., 2009), simple silicone membrane skin models (Khan et al., 2005; Waters et al., 2013) and most recently, chromatographic techniques (Hidalgo-Rodríguez et al., 2013). Simple models , such as a silicone membrane, are particularly suited to studies that require comparative values, for example, with variations in the presence of additional excipients or temperature changes (Waters et al., 2013) but may struggle to achieve absolute data. "
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    • "It should be remembered that the use of normal distribution can be theoretically justified in situations where a large number of effects act additively and independently together. The porous media, LBM and fluid factors used in these experiments can be a first approach to the effective permeability distribution of caffeine and testosterone solutions in silicone membrane (Khan et al., 2005). "
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    • "The former skin model has been shown to be an adequate model of human abdominal skin (Dick and Scott, 1992; Jacobi et al., 2007). The latter has been extensively used in screening tests (Khan et al., 2005). Yet, the relevance of using these models to screen for BC efficacy is not clearly established since there might be model specificity regarding the formulation–membrane interactions. "
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