Influence of d-limonene on the transdermal penetration of felodipine

Felodipine is a calcium antagonist, one of the dihydropyridines, with potential application in transdermal therapeutic systems (TTS). Earlier studies reported that the high lag time of this drug limited its potential development in a TTS. The present study analyzes the effect of d-limonene at concentrations of 0.5, 1, 5 and 10% on the transdermal penetration of this drug. The study was performed using a diffusion technique in vitro, with the skin of the hairless rat. d-Limonene significantly reduced the lag time (T1) to 1.4 h at a concentration of 1% (compared with 9.8 h in its absence). Higher concentrations did not produce a significant decrease in the value of this parameter. The presence of d-limonene in the formulae produces an increase in the permeability constant (Kp) and the flux (J). The relation between this increase and the percentage of d-limonene was non-linear. An asymptotic value was obtained at a concentration of 5%, with increases of 993% and 1570% for Kp and J, respectively.