IN-VITRO PULSATILE AND CONTINUOUS TRANSDERMAL DELIVERY OF BUSERELIN BY IONTOPHORESIS

Transdermal delivery of buserelin, a nonapeptide, from hydroxyethylcellulose hydrogel through isolated human stratum corneum was studied. In vitro studies were carried out in a drug release apparatus (DAB 10/USP XII) using self designed rotary disk cells equipped with platinum electrodes. Different forms of current were examined. A pulsatile application of continuous current resulted in a step-like permeation profile. Different on/off ratios (5 min/55 min; 10 min/50 min; 15 min/45 min) were studied. When continuous non-interrupted current with different current densities (0.1-0.3 mA.cm-2) was applied, linear dependence of the final cumulative amount of buserelin on current duration and density was observed. Passive permeation of buserelin through human stratum corneum was not detectable either before current flow or after a current period of 4 h (0.2 mA.cm-2). A comparison of iontophoretic release and passive release of buserelin from hydroxyethylcellulose hydrogel through a cellulose membrane showed matrix release for both. Iontophoretic enhancement was also significant for release behavior. In aqueous solution significant electrolysis was observed. Electrolysis of buserelin in hydrogel occurred less and was dependent on current density. The pH-shift in donor medium after electrically assisted permeation was examined for different current densities, current duration and ionic strength of buffer. The influence of donor pH and ionic strength on permeation was studied. Pulsed (2000 Hz; 0.1 mA.cm-2; square wave form) and continuous (0.1 mA.cm-2; 0.2 mA.cm-2) direct current were compared.