ENHANCING EFFECTS OF LIPOPHILIC VEHICLES ON SKIN PENETRATION OF METHYL NICOTINATE IN-VIVO

Vehicle effects may be caused by thermodynamic effects and by specific (penetration enhancing) effects. To investigate the effects of variou s lipophilic vehicles on drug penetration, an in vive permeability stu dy was conducted with methyl nicotinate as the model drug. The drug wa s dissolved in the respective vehicles at concentrations that provide equal drug escaping tendencies. Drug solutions were applied to the upp er arms of volunteers with a glass chamber system. To avoid drug deple tion effects, drug disappearance rates were measured under steady-stat e conditions by the difference method. Enhancement factors were calcul ated from the steady-state flux values (i.e., drug disappearance rates per area unit) and compared with results from non-steady-state experi ments. Significant enhancing effects (p < 0.01) were observed with dib utyl adipate, caprylic/capric acid triglycerides containing 5% phospho lipids, isopropyl myristate, and mineral oil. Caprylic/capric acid tri glycerides, cetearyl isooctanoate, and the standard vehicle dimethicon e 100 were without effect on drug penetration. The explanation for the observed enhancing effects may be an interaction of the lipophilic li quids with the lipid bilayers of the stratum corneum that leads to a d ecrease of the barrier resistance.