Physicochemical effects of terpenes on organogel for transdermal drug delivery

It is accepted that terpenes are effective penetration enhancers to promote the passage of drugs or chemicals through the human skin barrier. However the physical and chemical changes of a pharmaceutical vehicle induced by the incorporation of terpenes have not been explored. Thus, this study examines the effects of three terpenes (linalool, cineole, limonene) on the rheology and chemical stability of an organogel composed of dibutyllauroylglutamide (GP1) and propylene glycol (PG). At a given GP1 concentration, oxygen-containing linalool and cineole decreased gel moduli (elastic and viscous) and brittleness, and the reverse was obtained for hydrocarbon limonene. Probably, linalool and cineole interfered with hydrogen bonding between GP1 molecules while limonene could have initiated a phase separation-mediated gelation, changing the gel morphology. Microcalorimetry detected minute heat endotherms for gels (with and without terpenes) subjected to accelerated heat testing. These heat changes could arise from a small degree of structural disruption of the gel network. Heat endotherms normalized with respect to GP1 content were used to assess gel chemical stability. Although the terpenes altered rheology, they did not significantly affect the chemical stability of the gels. This is the first in the literature that reports the effect of penetration enhancers, such as terpenes, on the physical, rheological and chemical characteristics of a model pharmaceutical formulation for topical and transdermal drug delivery.