SUCROSE LAURATE GELS AS A PERCUTANEOUS DELIVERY SYSTEM FOR ESTRADIOL IN RABBITS

In this study sucrose laurate was formulated in hydrogels and investig ated as a suitable transdermal penetration enhancer for oestradiol. Us ing rabbits as an animal model, the absolute bioavailability and the s kin irritation were evaluated after single and multiple application. T hree hydrogels containing 60 mg% oestradiol were evaluated: Oestrogel, and two hypromellose gels containing 5 and 15% sucrose laurate (w/w), respectively. No stability problem of the sucrose laurate was detecte d during a storage period of four months at 7 +/- 2 degrees C. After s ingle application no significant difference (P < 0.05) was observed be tween the bioavailability parameters of Oestrogel and the 5% sucrose l aurate gel. The values obtained for the 15% sucrose laurate gel were s ignificantly higher than for the other gels. When applied on day 7 aft er a 6-day treatment, twice daily with the respective placebo gel, no significant difference was seen amongst the three formulations for any of the parameters evaluated. When the results after multiple applicat ion were compared with those after single application, a significant i ncrease in oestradiol bioavailability was seen for the gel containing 30% ethanol and a significant decrease in oestradiol bioavailability w as seen for the 5 and 15% sucrose laurate gels. Histological evaluatio n of the untreated and treated skin biopsies, showed a significantly h igher incidence of infiltrate for all treated skin biopsies in compari son with the untreated ones. A significant increase in skinfold thickn ess was seen for the skin biopsies treated with gel containing 15% suc rose laurate. It can be concluded that sucrose laurate shows a potenti al as an absorption enhancer for percutaneous drug delivery.