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 (Tl) 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.
Diez
I
I
Department of Pharmacy, University of Barcelona, Spain.
Peraire
C
C
Obach
R
R
Domenech
J
J
D000279:Administration, Cutaneous; D000818:Animals; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D053138:Cyclohexenes; D015736:Felodipine / Q000493:pharmacokinetics*; D000077222:Limonene; D010539:Permeability; D014677:Pharmaceutical Vehicles; D051381:Rats; D012867:Skin / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D013816:Thermodynamics
D002121:Calcium Channel Blockers; D053138:Cyclohexenes; D014677:Pharmaceutical Vehicles; D013729:Terpenes; D000077222:Limonene; D015736:Felodipine