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Validated models for predicting skin penetration from different vehicles.

Authors
Ghafourian-T; Samaras-EG; Brooks-JD; Riviere-JE
Source
Eur J Pharm Sci 2010 Dec; 41(5):612-616
NIOSHTIC No.
20038409
Abstract
The permeability of a penetrant though skin is controlled by the properties of the penetrants and the mixture components, which in turn relates to the molecular structures. Despite the well-investigated models for compound permeation through skin, the effect of vehicles and mixture components has not received much attention. The aim of this Quantitative Structure Activity Relationship (QSAR) study was to develop a statistically validated model for the prediction of skin permeability coefficients of compounds dissolved in different vehicles. Furthermore, the model can help with the elucidation of the mechanisms involved in the permeation process. With this goal in mind, the skin permeability of four different penetrants each blended in 24 different solvent mixtures were determined from diffusion cell studies using porcine skin. The resulting 96 kp values were combined with a previous dataset of 288 kp data for QSAR analysis. Stepwise regression analysis was used for the selection of the most significant molecular descriptors and development of several regression models. The selected QSAR employed two penetrant descriptors of Wiener topological index and total lipole moment, boiling point of the solvent and the difference between the melting point of the penetrant and the melting point of the solvent. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.454 for the logkp value of the test set.
Keywords
Absorption-rates; Biological-function; Chemical-properties; Dermatology; Exposure-assessment; Exposure-methods; Mathematical-models; Models; Qualitative-analysis; Risk-factors; Skin-absorption; Skin-exposure; Statistical-analysis; Toxins
Contact
Taravat Ghafourian, Medway School of Pharmacy, Universities of Kent and Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK
CODEN
EPSCED
Publication Date
20101223
Document Type
Journal Article
Email Address
t.ghafourian@kent.ac.uk
Funding Amount
746428
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007555
Issue of Publication
5
ISSN
0928-0987
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
European Journal of Pharmaceutical Sciences
State
NC
Performing Organization
North Carolina State University, Raleigh, North Carolina
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