Controlled drug release from polymeric delivery devices. III: In vitro-in vivo correlation for intravaginal release of ethynodiol diacetate from silicone devices in rabbits.
Forty female rabbits were implanted with silicone vaginal devices containing ethynodiol diacetate for up to 8 weeks. As predicted from in vitro studies, a Q - t1/2 (matrix-controlled) release profile was observed in vivo. The in vivo drug release profile was compared with in vitro data measured at three hydrodynamic conditions, and the diffusional resistance across the vaginal wall was estimated. Drug released from silicone devices yielded a prolonged plasma level when compared with data following intravaginal or intravenous administration of a solution dose. The rate constant for elimination was unchanged. The plasma concentration of the drug was related to the intravaginal drug release profile both theoretically and experimentally and was above the concentration required to inhibit fertilization.
D000818:Animals; D003273:Contraceptive Devices; D003429:Cross Reactions; D004058:Diffusion; D005040:Ethynodiol Diacetate / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D009640:Norethindrone / Q000097:blood; D011817:Rabbits; D011863:Radioimmunoassay; D012710:Serum Albumin, Bovine; D012828:Silicones; D013499:Surface Properties; D013997:Time Factors; D014621:Vagina / Q000378:metabolism
D012828:Silicones; D012710:Serum Albumin, Bovine; D005040:Ethynodiol Diacetate; D009640:Norethindrone