Zidovudinin transdermal uygulanmasında geçiş arttırma çalışmaları
No Thumbnail Available
Files
Date
2007
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Sağlık Bilimleri Enstitüsü
Abstract
In order to prepare formulations, polimethyl methacylate type polymers (Eudragit RL 100, RS 100) and ethyl cellulose polymers were used either alone or in combination with each other. Films were prepared by solvent evaporation method in stainless steel discs (3,6 cm in diameter). Each of the monolithic films includes 2,5 % w/w or 5 % w/w AZT and 25 % w/w dibuthyl sebacate of the dry polymer weight. HPLC and UV spectrophotometric analyses were used to determine amount of the drug in the films. Film thicknesses and diameters and in vitro and ex vivo release studies from films with franz diffusion method was performed. In vitro release study from films was studied with franz diffusion cells by using 0,22 ?m cellulose acetate membrane. The effect of polymer type on the in vitro release of zidovudine from films was performed and it was found that, the films that includes Eudragit RL 100 (%100 w/w) showed more rapid in vitro drug release among the formulations and films prepared by ethyl cellulose (%100 w/w) have the slowest in vitro drug release among the formulations. All the formulations were best fitted to Higuchi release kinetics. The effect of iontophoresis on the in vitro release of zidovudine was performed for 2 hours with 0,1 mA/cm2 and 0,5 mA/cm2 direct current by using Ag/AgCl electrodes and the results showed that the effect of iontophoresis on the release of zidovudine from the films were increased by increasing the current. In the ex vivo experiments, 5 cm2 dorsal skin of male wistar rats (250-300 weight) were used as membrane. These experiments were studied on the films coded as, AA14B (100 % Eudragit RL 100) and AA18B (Eudragit RL 100: Ethylcellulose (1:1) mixture) which were included the active substance at 5 % w/w. The passive diffusion of zidovudine from these films compared with iontophoresis application (0,1 mA/cm2 and 0,5 mA/cm2 current, DC current, Ag/AgCl electrode, 2 hours) and pre-treatment of chemical penetration enhancer (% 1 w/w and % 5 w/w DMSO solution, 2 hours). It was investigated that, the zidovudine amount transported from wistar rat skin increased by using these penetration enhancers. After 2 hours of iontophoresis application, it was found that the amount of zidovudine which transported from wistar rat skin was significantly increased by increasing the application current. Also the lag time for the study was significantly decreased. Significant difference was not found between effect of the 0,5 mA/cm2 iontophoresis and DMSO pre-treatment applications, in terms of zidovudine amount which transported to the receptor fluid. Also, no significant difference was found between the concentration effects of DMSO that applicated to wistar rat skin. The both enhancement methods were statistically have the same efficacy but the data obtained from iontophoresis application had smaller standard deviations then DMSO pre-treatment. This was the reason that we decided to enhance transdermal delivery of zidovudine by iontophoresis application in contrast with DMSO pre-treatment.
Description
Keywords
Dimetil sülfoksit, yontoforez, Transdermal Uygulamalar, Zidovudin, Dimethyl sulfoxide, Iontophoresis, Transdermal Applications, Zidovudine