Sucrose laurate gels as a percutaneous delivery system for oestradiol in rabbits.
In this study sucrose laurate was formulated in hydrogels and investigated as a suitable transdermal penetration enhancer for oestradiol. Using rabbits as an animal model, the absolute bioavailability and the skin irritation were evaluated after single and multiple application. Three 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 detected during a storage period of four months at 7 +/- 2 degrees C. After single application no significant difference (P < 0.05) was observed between the bioavailability parameters of Oestrogel and the 5% sucrose laurate gel. The values obtained for the 15% sucrose laurate gel were significantly higher than for the other gels. When applied on day 7 after 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 application were compared with those after single application, a significant increase in oestradiol bioavailability was seen for the gel containing 30% ethanol and a significant decrease in oestradiol bioavailability was seen for the 5 and 15% sucrose laurate gels. Histological evaluation of the untreated and treated skin biopsies, showed a significantly higher incidence of infiltrate for all treated skin biopsies in comparison with the untreated ones. A significant increase in skinfold thickness was seen for the skin biopsies treated with gel containing 15% sucrose laurate. It can be concluded that sucrose laurate shows a potential as an absorption enhancer for percutaneous drug delivery.
Vermeire
A
A
Laboratory of Pharmaceutical Technology, University of Gent, Belgium.
De Muynck
C
C
Vandenbossche
G
G
Eechaute
W
W
Geerts
M L
ML
Remon
J P
JP
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000431:Ethanol / Q000737:chemistry; D005782:Gels; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D012869:Skin Absorption; D012885:Skinfold Thickness; D012995:Solubility; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry
D005782:Gels; C018152:sucrose monolaurate; D000431:Ethanol; D004958:Estradiol; D013395:Sucrose