Simple rules defining the potential of compounds for transdermal delivery or toxicity
Date
2004
Authors
Magnusson, B.
Pugh, W.
Roberts, M.S.
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Advisors
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Volume Title
Type:
Journal article
Citation
Pharmaceutical Research, 2004; 21(6):1047-1054
Statement of Responsibility
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Abstract
<h4>Purpose</h4>Simple rules based on readily accessible physicochemical properties enable identification of solutes that penetrate skin very slowly or rapidly.<h4>Methods</h4>Literature in vitro maximal flux values (Jmax) across human skin were collected for 87 penetrants. Penetrants were assigned as "good" (Jmax > 10(-5.52) mole x cm(-2) x h(-1)), "bad" (Jmax < 10(-8.84) mole x cm(-2) x h(-1)) or "intermediate" based on mean +/- 1SD. The feasibility of using readily available physicochemical properties, such as molecular weight (MW), melting point (MP, degrees K), octanol-water partition coefficient (K), water solubility (S, molarity), number of atoms available for H-bonding (HB), in assigning solutes was examined.<h4>Results</h4>Good penetrants had MW < or = 152, log S > -2.3, HB < or = 5, log K < 2.6, MP < or = 432. Bad penetrants had MW > 213, log S < -1.6, HB > or = 4, log K > 1.2, MP > or = 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.<h4>Conclusions</h4>These rules enable rapid screening of potential drug delivery candidates and environmental exposure risks.