Combination strategies to enhance transdermal permeation of zidovudine (AZT).
The objective of this study was to evaluate the effect of simultaneous application of two penetration enhancers of different chemical classes or a chemical penetration enhancer and current application on permeation of zidovudine (AZT) across rat skin. Ex vivo permeation of AZT using combinations of cineole or menthol in vehicle with either oleic acid/linolenic acid or 0.5 mA/cm2 anodal current application for 6 h was studied. Penetration enhancers were significantly different in enhancing the permeability of AZT across rat skin and are in the decreasing order of activity: linolenic acid > menthol > oleic acid > cineole > vehicle. The combination of cineole and oleic acid synergistically enhanced transdermal flux of AZT in addition to reducing lag time. However, this was not observed for combinations of menthol with oleic or linolenic acid. On the other hand, the simultaneous application of current with menthol and cineole significantly increased cumulative amounts of AZT permeating during the course of current application and reduced the lag time but failed to further increase steady state flux of AZT. These results suggest that a combination of two penetration enhancers of different classes or the simultaneous use of iontophoresis and a penetration enhancer may be advantageous to achieve permeation enhancement with low risk of skin damage.
Thomas
N S
NS
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Punjab, India.
Panchagnula
R
R
D000279:Administration, Cutaneous; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003511:Cyclohexanols; D004558:Electric Stimulation; D000077591:Eucalyptol; D005079:Excipients; D005227:Fatty Acids; D066298:In Vitro Techniques; D007478:Iontophoresis; D008610:Menthol; D039821:Monoterpenes; D019301:Oleic Acid; D010592:Pharmaceutic Aids; D014677:Pharmaceutical Vehicles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D003511:Cyclohexanols; D005079:Excipients; D005227:Fatty Acids; D039821:Monoterpenes; D010592:Pharmaceutic Aids; D014677:Pharmaceutical Vehicles; D008610:Menthol; D019301:Oleic Acid; D015215:Zidovudine; D000077591:Eucalyptol