Enhancement of transdermal delivery by superfluous thermodynamic potential. II. In vitro-in vivo correlation of percutaneous nifedipine transport.
Nifedipine was selected as a representative compound to investigate a method for improving transdermal bioavailability. The general strategy explored to improve the percutaneous transport of nifedipine was the manipulation of thermodynamics of the drug substance by the use of volatile/nonvolatile systems as vehicles. To investigate the potential of the strategy, diffusion studies were conducted using an ethylene-vinyl acetate copolymer (EVA) membrane and full-thickness excised abdominal skin of rats. Little penetration through EVA membrane or rat skin was found either from the volatile solvent ethanol (EtOH) or from the nonvolatile solvent diethyl sebacate (DES). When the vehicle was changed to a mixed solvent containing both EtOH and DES in a volume ratio of 75:25, penetration through EVA membrane or rat skin was increased up to 3 to 4 times, compared with those values for DES. The increase in the penetration was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The bioavailability of percutaneous nifedipine in rats was determined from the drug solutions containing different proportions of EtOH and DES. Once again, the highest bioavailability was achieved from the mixed solvent containing EtOH and DES in a volume ratio of 75:25. The area under the plasma nifedipine concentration-time curve for the mixed solvent was higher by about 4 times than that for DES.
Kondo
S
S
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Yamasaki-Konishi
H
H
Sugimoto
I
I
D000279:Administration, Cutaneous; D000818:Animals; D004058:Diffusion; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
D009543:Nifedipine