In vitro release and permeation kinetics of Melaleuca alternifolia (tea tree) essential oil bioactive compounds from topical formulations

Melaleuca alternifolia essential oil (tea tree oil, TTO) is well known for its antimicrobial, antifungal and anti-inflammatory properties, which it is currently used as an active ingredient in skin care products. This study investigates and evaluates the permeation and release kinetics of TTO marker compounds from several semisolid formulations (creams, ointments, gels) containing TTO in different percentages (5-30% w/w). In vitro permeation and release tests were run in vertical Franz diffusion cells with synthetic and pig-skin membranes for different times (from 10minutes to 50hours). The recovered receiving phases were analyzed by Headspace Solid-Phase Microextraction (HS-SPME) in combination with Gas Chromatography coupled with Mass Spectrometry (GC-MS). The method adopted is completely automatic and provides on-line monitoring of the release and permeation kinetics, while avoiding time-consuming solvent extraction. The study examined both the total amount of essential oil and some selected markers known to be responsible for TTO's biological activities, i.e. 1,8-cineole, 4-terpineol and alpha-terpineol. The results of in vitro release and permeation tests demonstrated that all compounds show the same kinetics profiles, although amount released differs significantly. The markers were quantified by external calibration curves constructed through HS-SPME-GC-MS. Some preliminary experiments were also run to monitor the presence of the above markers within the skin.