Studies on transdermal delivery enhancement of zidovudine.
The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm(2) area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm(2) direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm(2) current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm(2) current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine.
Takmaz
Evrim Atilay
EA
Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Tandoğan, Ankara, Turkey.
Inal
Ozge
O
Baykara
Tamer
T
D000096:Acetone / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D007478:Iontophoresis; D007700:Kinetics; D008297:Male; D000432:Methanol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D015215:Zidovudine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
D000180:Acrylic Resins; D019380:Anti-HIV Agents; D004337:Drug Carriers; D012997:Solvents; D000096:Acetone; C050528:Eudragit RS; D015215:Zidovudine; C013517:ethyl cellulose; D002482:Cellulose; D000432:Methanol; D004121:Dimethyl Sulfoxide