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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    ABSTRACT: This study evaluates the potential application of micellar liquid chromatography (MLC) to predict skin permeation with a series of model compounds. MLC has previously been found to be useful in the prediction of partition coefficient values (logP) for pharmaceutical compounds, yet has not been incorporated in skin permeability models prior to this work. This article provides statistically supported data that this technique enhances the ability to predict the permeability of similar drugs through the skin (Kp). The replacement of a traditional physicochemical parameter, namely the octanol-water partition coefficient (logPow) with a chromatographically determined value (logPmw), results in a quantitative partition-permeability relationship that is robust to variation. MLC offers many benefits compared with the traditional techniques employed to obtain logP values.
    European Journal of Pharmaceutical Sciences 08/2013; DOI:10.1016/j.ejps.2013.08.002 · 3.01 Impact Factor
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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). "
    Petrochemicals, 03/2012; , ISBN: 978-953-51-0411-7
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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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    ABSTRACT: Prevention of exposure to the neurotoxic organophosphorus compounds (OP) is a major concern both for pesticide users and soldiers. Skin barrier creams are being developed to complement or replace uncomfortable chemical protective suits. Quick evaluation of formulations efficacy mainly relies on in vitro tests which lead to consistent, complementary and relevant results. The objectives of this work were to determine the consistency of results from in vitro tests and importance of the formulation composition in the skin protective efficacy. The efficacy of three formulations, i.e. oil-in-water and water-in-oil emulsions and perfluorinated compounds-based cream, was evaluated against the OP paraoxon in vitro. Our results indicated that the least effective formulations could be quickly identified by performing in vitro permeation tests with silicone membrane and by evaluating interfacial interactions between formulations and OP. Among the tested formulations, the perfluorinated compounds-based cream could have a broader spectrum of efficacy than emulsions against OP and other toxic chemicals.
    Toxicology in Vitro 11/2008; 23(1):127-33. DOI:10.1016/j.tiv.2008.09.014 · 3.21 Impact Factor
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