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Linear combination methods for prediction of drug skin permeation
Scheler, S. Fahr, A. Liu, Xiangli
Scheler, S.
Fahr, A.
Liu, Xiangli
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2015-01
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©2014 by the authors; licensee IAPC, Zagreb, Croatia. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)
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Abstract
Many in-vitro methods for prediction of skin permeability have been reported in literature. Cerasome electrokinetic chromatography is one of the most sophisticated approaches representing a maximum level of similarity to the lipid phase of the stratum corneum. One goal of this study was to investigate the affinity pattern of Cerasome and to compare it with the permeability profile of human skin. Another purpose was to study the applicability of Hansen solubility parameters for modelling skin permeation and to investigate the predictive and explanatory potential of this method. Visualisation in Hansen diagrams revealed very similar profiles of Cerasome electrokinetic chromatography retention factors and skin permeability coefficients. In both cases, the characteristic pattern with two clusters of highly retained or highly permeable substances could be shown to be mainly caused by two groups of compounds, one of them with high affinity to ceramides, fatty acids and lecithin and the other being more affine to cholesterol. If based on a sufficiently comprehensive experimental dataset, model-independent predictions of skin permeability data using three-component Hansen solubility parameters are able to achieve similar accuracy as calculations made with an Abraham linear free energy relationship model in which the compounds are characterized by seven physicochemical descriptors.
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Scheler S, Fahr A and Liu X (2014) Linear combination methods for prediction of drug skin permeation. ADMET and DMPK. 2(4): 199-220.
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