A hydroxyapatite ceramic matrix device for continuous delivery of coumadin

Coumadin is one of the most widely used oral anticoagulants for preventing several types of thromboembolic complications. However, coumadin, when given in dosages which maintain the plasma levels slightly above the effective threshold, has been associated with severe side effects such as excessive hemorrhaging and necrosis. Development of an implantable, biodegradable hydroxyapatite ceramic device for continuous delivery of effective amounts of coumadin should alleviate these side effects. The ceramic devices used in this experiment consisted of 400 mg HA and 100 mg coumadin compressed at loads of 3000, 6000, and 9000 lbs. in a hydraulic press. The ceramic devices released their entire anticoagulant content within 12 hours, with a linear release for the first four hours. Ceramics compressed at different loads released significantly different amounts of coumadin for the first four hours of the experiment. Since the amounts of drug released in one day in vitro are released for almost 10 to 15 days in vivo, the data obtained in this study suggest that hydroxyapatite ceramic matrix implants containing 100 mg coumadin should release the anticoagulant continuously for a minimum of 10 days in vivo.