In vitro studies on release and human skin permeation of Australian tea tree oil (TTO) from topical formulations

Eur J Pharm Biopharm. 2006 Oct;64(2):222-8. doi: 10.1016/j.ejpb.2006.05.006. Epub 2006 May 23.


Essential oils are widely used in pharmaceutical and cosmetic preparations e.g. as fragrance, active ingredient or penetration enhancer. However, reports on skin absorption are rare. Therefore, the aim of our study was to investigate the capability of terpinen-4-ol, the main compound of Australian tea tree oil (TTO), to permeate human skin. In static Franz diffusion cells permeation experiments with heat separated human epidermis were carried out using infinite dosing conditions and compared to liberation experiments. The flux values of three different semisolid preparations with 5% TTO showed the rank order semisolid O/W emulsion (0.067 microl/cm2 h) > white petrolatum (0.051 microl/cm2 h) > ambiphilic cream (0.022 microl/cm2 h). In comparison to the flux value obtained with the native TTO (0.26 microl/cm2 h), the flux values are remarkably reduced due to the lower amount of terpinen-4-ol. P(app) values for cream (2.74+/-0.06 x 10(-7) cm/s) and native TTO (1.62+/-0.12 x 10(-7) cm/s) are comparable whereas white petrolatum (6.36+/-0.21 x 10(-7) cm/s) and semisolid O/W emulsion (8.41+/-0.15 x 10(-7) cm/s) demonstrated higher values indicating a penetration enhancement. No relationship between permeation and liberation was found.

MeSH terms

  • Administration, Cutaneous
  • Australia
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / chemistry
  • Dermatologic Agents / pharmacokinetics
  • Diffusion
  • Diffusion Chambers, Culture
  • Emulsions
  • Epidermis / metabolism
  • Female
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Ointments
  • Permeability
  • Skin / metabolism*
  • Skin Absorption / physiology*
  • Tea Tree Oil / administration & dosage
  • Tea Tree Oil / chemistry
  • Tea Tree Oil / pharmacokinetics*
  • Terpenes / administration & dosage
  • Terpenes / chemistry
  • Terpenes / pharmacokinetics


  • Dermatologic Agents
  • Emulsions
  • Ointments
  • Terpenes
  • terpinenol-4
  • Tea Tree Oil