The effect of terpene enhancer lipophilicity on the percutaneous permeation of hydrocortisone formulated in HPMC gel systems

The percutaneous permeation of hydrocortisone (HC) was investigated in hair less mouse skin after application of an alcoholic hydrogel using a diffusio n cell technique. The formulations contained one of 12 terpenes, the select ion of which was based on an increase in their lipophilicity (log P 1.06 - 5.36). Flux, cumulative receptor concentrations, skin content, and lag time of HC were measured over 24 h and compared with control gels (containing n o terpene). Furthermore, HC skin content and the solubility of HC in the al coholic hydrogel solvent mixture in the presence of terpene were determined , and correlated to the enhancing activity of terpenes. The in vitro permea tion experiments with hairless mouse skin revealed that the terpene enhance rs varied in their ability to enhance the flux of HC. Nerolidol which posse ssed the highest lipophilicity (log P = 5.36 +/- 0.38) provided the greates t enhancement for HC flux (35.3-fold over control). Fenchone (log P = 2.13 +/- 0.30) exhibited the lowest enhancement of HC flux (10.1-fold over contr ol). In addition, a liner relationship was established between the log P of terpenes and the cumulative amount of HC in the receptor after 24 h (Q(24) ). Nerolidol, provided the highest Q(24) (1733 +/- 93 mu g/cm(2)), whereas verbenone produced the lowest Q(24) (653 +/- 105 mu g/cm(2)). Thymol provid ed the lowest HC skin content (1151 +/- 293 mu g/g), while cineole produced the highest HC skin content (1899 +/- 5666 mu g/g). No correlation was est ablished between the log P of enhancers and HC skin content. A correlation however, existed between the log P terpenes and the lag time. As lag P incr eased, a linear decrease in lag time was observed. Cymene yielded the short est HC lag time, while fenchone produced the longest lag time. Also, the in crease in the log P of terpenes resulted in a proportional increase in HC s olubility in the formulation solvent mixture. (C) 2000 Elsevier Science B.V . All rights reserved.