Synthesis and investigation of urea compounds as transdermal penetration enhancers

Donald A. Godwin, Mark R. Player, J. Walter Sowell, Bozena B. Michniak

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26 Scopus citations


Twelve urea and thiourea compounds were examined for their transdermal penetration enhancing properties in vitro using hairless mouse skin and hydrocortisone as a model drug. Skins were pretreated for 1 h with the enhancer in propylene glycol before application of the drug also in propylene glycol. Enhancement ratios (ER) were calculated for permeability coefficient (P), 24 h receptor concentration (Q24), and skin content of drug (SC) and compared to control values (no enhancer present). Control values for permeability coefficients were 0.71 ± 0.27 cm h-1, 24 h receptor concentration: 11.9 ± 3.4 μM, and skin content of drug 44.6 ± 18.5 μg g- 1. The most effective enhancer of the series was 1-dodecyl-3-methylthiourea. This enhancer produced the highest values for all three penetration parameters with a permeability coefficient 4.7 ± 1.8 x 10-4 cm h-1 (ER(P) 6.6), a 24 h receptor concentration of 62.7 ± 16.3 μM (ER(Q24) 5.3), and a skin content of 90.1 ± 17.7 μg g-1 (ER(SC) 2.0). A structure- activity relationship was observed in that the thio-substituted analogs were more effective enhancers than the oxygen-containing compounds. Although these compounds show promise as penetration enhancers, further study is needed to determine their effectiveness with other drugs and their irritation potential.

Original languageEnglish (US)
Pages (from-to)165-175
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Jun 1 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Hairless mouse
  • Hydrocortisone
  • Percutaneous penetration
  • Skin retention
  • Transdermal drug delivery
  • Ureas


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