In vitro permeation and in vivo pharmacokinetics of once-weekly contraceptive patch containing gestodene and ethinlyestradiol

The aim of this study was to prepare the once-weekly contraceptive patch containing gestodene (GSD) and ethinlyestradiol (EE) and to study its in vitro and in vivo characterization. A method for determination of GSD and EE in vitro by HPLC was established, and permeation tests were conducted in mouse skin. Release tests were conducted according to Chinese Pharmacopoeia. The plasma-concentrations of GSD and EE were determined by LC-MS/MS and GC-MS, respectively, so as to study the pharmacokinetic behavior of transdermal patches in rabbits. The in vitro transdermal permeation of both drugs from the patches displayed a zero-order process, permeation rate constants were 0. 377 μg/( cm ^2·h) for GSD, and 0. 092 μg/( cm ^2·h) for EE. The in vitro release profiles of both drugs were in accordance with Higuchi equation and the cumulative release percentages in 168 hours were 90. 7% and 92. 2%, respectively. After administration of compound GSD patches and commercial tablets in rabbits, c _max of GSD were (4. 44±0. 24) and (8. 43±2. 15) ng/mL; t _max were (12. 50±1. 96) and (0. 20±0. 05) h; AUC were (1 029. 25±91. 58) and (311. 84±100. 88) ng/mL·h, respectively. C _max of EE were (2. 63± 0.13) and (7. 85±1.73) ng/mL; t _max were (48. 44±7. 61) and (0. 25±0. 02) h; AUC were (752. 40±62. 91) and (216. 10±56. 83) ng/mL·h, respectively. Compared with commercial tablets, c _max of patches of both drugs were reduced, while t _max were prolonged and AUC were enhanced. The results showed that the once-weekly contraceptive patch could maintain the drug release through rabbit skin for at least 7 days. The novel prepared patch might be a promising non-oral contraceptive preparation.