Pharmaceutical Research

, Volume 23, Issue 5, pp 912–919 | Cite as

Synthesis and Enhancing Effect of Transkarbam 12 on the Transdermal Delivery of Theophylline, Clotrimazole, Flobufen, and Griseofulvin

  • Alexandr Hrabálek
  • Pavel Doležal
  • Kateřina Vávrová
  • Jarmila Zbytovská
  • Tomáš Holas
  • Jana Klimentová
  • Jakub Novotný
Research Paper

Purpose

Dodecyl-6-aminohexanoate (DDEAC) is a transdermal permeation enhancer with excellent activity, low toxicity, and no dermal irritation. We hypothesized that DDEAC reacts with air CO2 to form a two-chain ammonium carbamate—Transkarbam 12 (T12)—which is responsible for the enhancing effect.

Methods

DDEAC and T12 were synthesized, their structures were confirmed by spectral methods, and their enhancing activity was studied using the Franz diffusion cell and human skin. A high-performance liquid chromatography method was developed for determination of T12, and its biodegradability was evaluated using porcine esterase.

Results

Only the carbamate salt T12 was responsible for the high enhancing activity; DDEAC tested under argon to avoid reaction with CO2 was inactive. T12 enhanced transdermal permeation of drugs covering a wide range of physicochemical properties, including theophylline (enhancement ratio up to 55.6), clotrimazole (7.7), flobufen (5.0), and griseofulvin (24). The activity was pH-dependent, further confirming the importance of the carbamate structure. The metabolization of T12 followed a second-order kinetics with t1/2 = 31 min.

Conclusion

Our results indicate that T12 is a promising biodegradable permeation enhancer for a wide range of drugs, and the structurally novel group of carbamate enhancers warrants further investigation.

Key Words

ammonium carbamate biodegradability permeation enhancer transdermal drug delivery 

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Alexandr Hrabálek
    • 1
    • 2
  • Pavel Doležal
    • 3
  • Kateřina Vávrová
    • 1
    • 2
  • Jarmila Zbytovská
    • 3
  • Tomáš Holas
    • 1
  • Jana Klimentová
    • 1
  • Jakub Novotný
    • 1
  1. 1.Department of Inorganic and Organic Chemistry, Faculty of PharmacyCharles University in PragueHradec KrálovéCzech Republic
  2. 2.Centre for New Antivirals and Antineoplastics, Faculty of PharmacyCharles University in PragueHradec KrálovéCzech Republic
  3. 3.Department of Pharmaceutical Technology, Faculty of PharmacyCharles University in PragueHradec KrálovéCzech Republic

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