Effect of vehicles and enhancers on the topical delivery of cyclosporin A.
Topical delivery of cyclosporin a (CysA) is of great interest for the treatment of autoimmune skin disorders. The purpose of this study was to investigate the effect of various vehicles and enhancers on the topical delivery across rat skin. The topical (to the skin) delivery of CysA was evaluated in vitro using rat skin mounted in a Franz diffusion cell. CysA was analyzed by UV-HPLC. As vehicles, CysA vehicle containing 40% ethanol showed significantly enhanced deposition of CysA into the stratum corneum (SC) and deeper skin, as compared to other vehicles. The efficiency of the vehicles to improve the topical delivery of CysA was sequenced in the order of: 40% ethanol>ethyl oleate>Transcutol>isopropyl myristate>ethanol>Labrasol>propylene glycol>Lauroglycol FCC. Next, we tested effect of pre-treatment with chemical enhancers on the penetration of CysA. The permeation-enhancer effect of enhancers was in the following order: 10% menthol approximately 0.05% SLS>5% Azone>5% NMP>5% DEMO. Moreover, chemical enhancers shortened the lag time of the penetration of CysA into deeper skin. The present study suggests that the suspension of 40% ethanol containing 0.5% drug can more effectively enhance the topical delivery of CysA after skin pre-treatment with 10% menthol or 0.05% SLS.
Liu
Hongzhuo
H
School of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua RD NO 103, Shenyang 110016, People's Republic of China.
Li
Sanming
S
Wang
Yongjun
Y
Yao
Huimin
H
Zhang
Yan
Y
D000287:Administration, Topical; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage* / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D000431:Ethanol / Q000494:pharmacology; D005026:Ethylene Glycols / Q000494:pharmacology; D008297:Male; D008610:Menthol / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology; D010539:Permeability; D014677:Pharmaceutical Vehicles; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors
D005026:Ethylene Glycols; D009829:Oleic Acids; D014677:Pharmaceutical Vehicles; D012997:Solvents; D013501:Surface-Active Agents; D008610:Menthol; D012967:Sodium Dodecyl Sulfate; D000431:Ethanol; D016572:Cyclosporine; C010111:carbitol; C033180:ethyl oleate