Differential effects of some natural compounds on the transdermal absorption and penetration of caffeine and salicylic acid.

Many natural products have the potential to modulate the dermal penetration of topically applied drugs and chemicals. We studied the effect of five natural compounds (hydroxycitronellal, limonene 1,2-epoxide, terpinyl acetate, p-coumaric acid, transferrulic acid) and ethanol on the transdermal penetration of two marker drugs ((14)C-caffeine and (14)C-salicylic acid) in a flow through in vitro porcine skin diffusion system. The parameters of flux, permeability, diffusivity, and percent dose absorbed/retained were calculated and compared. The dermal absorption of (14)C-caffeine was significantly higher with terpinyl acetate and limonene 1,2-epoxide as compared to ethanol; while dermal absorption of (14)C-salicylic acid was significantly greater with hydroxycitronellal and limonene 1,2-epoxide as compared to ethanol. A 10-fold increase in flux and permeability of caffeine with terpinyl acetate was observed while limonene increased flux of caffeine by 4-fold and permeability by 3-fold. Hydroxycitronellal and limonene increased salicylic acid's flux and permeability over 2-fold. The other natural compounds tested did not produce statistically significant effects on dermal penetration parameters for both caffeine and salicylic acid (p≥0.05). These results emphasize the differential effects of natural substances on the transdermal penetration of hydrophilic (caffeine) and hydrophobic (salicylic acid) drugs.