A hydroxyapatite system for the continuous release of coumadin an anticoagulant

Coumadin is an anticoagulant used in the treatment of patients with pulmonary thromboembolisms or those implanted with mechanical vascular devices. Its efficacy is complicated by side effects such as hemorrhaging. Administration of coumadin by the traditional routes of pills and injections causes wide fluctuations of the drug in plasma. Thus, experiments were conducted to develop a hydroxyapatite ceramic system for releasing coumadin in vivo continuously for 7-10 days. A series of preliminary in vivo experiments was conducted to determine an effective non-lethal therapeutic dosage of coumadin for rats. Homogenous matrices containing varying amounts of coumadin were implanted subcutaneously in rats and the blood clotting time was determined. Results of these experiments showed that one mg coumadin delivered from HA implants doubled the blood clotting time and did not induce fatal hemorrhage. Subsequent in vitro studies were conducted to determine the most efficient way to deliver coumadin at a slow and sustained rate. Results of these experiments suggested that a solid insert of one mg of compressed coumadin in a hydroxyapatite ceramic shell released the drug more slowly and efficiently than a homogenous matrix consisting of compressed coumadin and hydroxyapatite.