Double-layer patch containing gestodene and ethinylestradiol :preparation and in vitro/in vivo characterization / 中国药科大学学报

ABSTRACT

Aim: To prepare a novel contraceptive patch containing gestodene(GEST) and ethinylestradiol(EE), and to study the in vitro characterization and in vivo contraceptive effect. Methods: Double-layer technique was applied to sustain steady 7-day permeation flux of drugs. Polariscope examination was carried out to observe the drug distribution behavior in the patch. Uniformity, adhesion, skin irritation, release and permeation tests were conducted to evaluate in vitro characterization. Anti-implantation and anti-fertility experiments were carried out to investigate its contraceptive effect. Results: The in vitro release profiles of both drugs were in accordance with Higuchi equation. The daily permeated amount of GEST per 10 cm2 patch was about 75 μg while the amount of EE was 30 μg.The in vitro transdermal permeation of both drugs from the patches displayed a zero-order process. Permeation rate constants were 0. 377 μg/(cm2·h) for GEST, and 0. 092 μg/(cm2· h) for EE, respec-tively. After transdermal administration, the embryonic number of the test groups was zero, and the uterus coefficients of those groups were significantly reduced compared with those of the control group (P < 0. 01). Conclusion: Double-layer transdermal drug delivery system(TDDS) could allow the steady 7-day permeation flux of drugs when the drug ratio between the immediate-release layer and the reservoir layer was 14. In vivo charac-terization demonstrated its contraceptive effects. The prepared novel patch might be a promising non-oral contra-ceptive preparation.