Simple rules defining the potential of compounds for transdermal delivery or toxicity

Magnusson, Beatrice M., Pugh, W.John and Roberts, Michael S. (2004) Simple rules defining the potential of compounds for transdermal delivery or toxicity. Pharmaceutical Research, 21 6: 1047-1054. doi:10.1023/B:PHAM.0000029295.38564.e1


Author Magnusson, Beatrice M.
Pugh, W.John
Roberts, Michael S.
Title Simple rules defining the potential of compounds for transdermal delivery or toxicity
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
Publication date 2004-01-01
Year available 2004
Sub-type Article (original research)
DOI 10.1023/B:PHAM.0000029295.38564.e1
Open Access Status
Volume 21
Issue 6
Start page 1047
End page 1054
Total pages 8
Editor V. H. L. Lee
Place of publication USA
Publisher Plenum Publishing Corporation
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730117 Skin and related disorders
Abstract Purpose. Simple rules based on readily accessible physicochemical properties enable identification of solutes that penetrate skin very slowly or rapidly.
Formatted abstract
Purpose. Simple rules based on readily accessible physicochemical properties enable identification of solutes that penetrate skin very slowly or rapidly.
Methods. Literature in vitro maximal flux values (Jmax) across human skin were collected for 87 penetrants. Penetrants were assigned as ldquogoodrdquo (Jmax > 10-5.52 mole·cm-2·h-1), ldquobadrdquo (Jmax < 10-8.84 mole·cm-2·h-1) or ldquointermediaterdquo based on mean ± 1SD. The feasibility of using readily available physicochemical properties, such as molecular weight (MW), melting point (MP,°K), octanol-water partition coefficient (K), water solubility (S, molarity), number of atoms available for H-bonding (HB), in assigning solutes was examined.
Results. Good penetrants had MW le 152, log S > -2.3, HB le 5, log K < 2.6, MP le 432. Bad penetrants had MW > 213, log S < -1.6, HB ge 4, log K > 1.2, MP ge 223. Discriminant analysis using MW, HB, log K correctly assigned 70% of compounds. Individual success rates were good (88%), intermediate (58%), bad (93%). Aqueous Jmax data for 148 test solutes were used for validation. Discriminant analysis assigned 76% of compounds, with individual rates of good (76%), intermediate (67%), and bad (97%). No good penetrants were misclassified as bad or vice versa.
Conclusions. These rules enable rapid screening of potential drug delivery candidates and environmental exposure risks.
Keyword Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Multivariate Data Analysis
Quantitative Structure-activity Relationships
Transdermal Absorption
Penetrant Structure Relationships
Skin Permeability Coefficients
Epidermal Permeability
Stratum-corneum
Molecular-size
Diffusion
Parameters
Qsar
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 33 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 13:31:40 EST