In vivo quantification of acyclovir exposure in the dermis following iontophoresis of semisolid formulations

J Pharm Sci. 2009 Mar;98(3):917-25. doi: 10.1002/jps.21474.

Abstract

The objective was to quantify acyclovir (ACV) exposure in the dermis following iontophoresis of nontraditional (pH-11 gels) and traditional (neutral cream) topical formulations of ACV. Given that the application time of a formulation on the skin can be significantly reduced with iontophoresis, the use of formulations optimized for iontophoretic delivery was explored to maximize the delivery of ACV to the site of action for the treatment of Herpes-labialis. Microdialysis probes were inserted into the shaved skin of tranquilized rabbits. Iontophoresis was performed at a constant current density of 200 microA/cm(2) for 60 min using a single-use drug cartridge filled with the following formulations: neutral cream, soluble fraction of the same cream (anodal and cathodal-current), or two formulations of pH-11 gels, one without and one with stabilizers and preservatives (cathodal-current). Results showed that only the ACV in the water phase of the cream is available for transport. All of the pH-11 gels exhibited a statistically significant (p < 0.001) increase in ACV dermis exposure compared to the neutral cream formulations without any additional sign of skin irritation. In conclusion, iontophoresis of ACV pH-11 gels provides higher ACV concentrations in the dermis than iontophoresis of neutral cream formulations, which could result in a better clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / administration & dosage*
  • Acyclovir / pharmacokinetics
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • Female
  • Hydrogen-Ion Concentration
  • Iontophoresis / methods
  • Microdialysis
  • Ointments / administration & dosage*
  • Ointments / chemistry*
  • Ointments / pharmacokinetics
  • Rabbits
  • Skin / metabolism*

Substances

  • Antiviral Agents
  • Ointments
  • Acyclovir