The feasibility of using 10% 1,8-cineole as an enhancer for transdermal delivery of haloperidol has been examined. In-vitro transdermal delivery across full-thickness human, rabbit and hairless mouse skins was measured from three polymer gel systems, hypromellose (hydroxypropylmethylcellulose), Carbomer (Carbopol) 940 and macrogol (polyethylene glycol) using Franz cells. Values for the permeability coefficient kp, calculated as the product (Kh)x(D/h2) where these two factors were obtained from curve fitting of the non-steady-state equation over 24 h, were similar from the three formulations. The value of kp from hypromellose was significantly enhanced by cineole by factors of 6.2 (4.6-8.1), 5.6 (5.0-6.2) and 3.0 (2.6-3.4) for human, rabbit and mouse, respectively (mean and 95% confidence intervals). Enhancement ratios for K: 13.3 (8.3-20), 3.1 (2.5-3.9) and 2.0 (1.5-2.6), were higher than those for D: 0.47 (0.41-0.55), 1.8 (1.6-2.1) and 1.5 (1.3-1.8). This suggested that the barrier function of the skin lipids was marginally affected and the main effect was to increase the thermodynamic activity of the drug in the barrier. The enhancement achieved in human skin suggested that delivery could be safely enhanced by terpenoids.

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