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 various lipophilic vehicles on drug penetration, an in vivo permeability study was conducted with methyl nicotinate as the model drug. The drug was dissolved in the respective vehicles at concentrations that provide equal drug escaping tendencies. Drug solutions were applied to the upper arms of volunteers with a glass chamber system. To avoid drug depletion effects, drug disappearance rates were measured under steady-state conditions by the difference method. Enhancement factors were calculated from the steady-state flux values (i.e., drug disappearance rates per area unit) and compared with results from non-steady-state experiments. Significant enhancing effects (p < 0.01) were observed with dibutyl adipate, caprylic/capric acid triglycerides containing 5% phospholipids, isopropyl myristate, and mineral oil. Caprylic/capric acid triglycerides, cetearyl isooctanoate, and the standard vehicle dimethicone 100 were without effect on drug penetration. The explanation for the observed enhancing effects may be an interaction of the lipophilic liquids with the lipid bilayers of the stratum corneum that leads to a decrease of the barrier resistance.
Leopold
C S
CS
Department of Pharmaceutical Technology, Heinrich-Heine-University, Düsseldorf, Germany.
Lippold
B C
BC
D000328:Adult; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008875:Middle Aged; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013268:Stimulation, Chemical
D008051:Lipid Bilayers; D008055:Lipids; D009539:Nicotinic Acids; D014677:Pharmaceutical Vehicles; C008473:methyl nicotinate