Continuous delivery of azidothymidine by hydroxyapatite or tricalcium phosphate ceramics

A ceramic drug delivery system was developed for continuous release of azidothymidine (AZT). Tricalcium phosphate (TCP) and hydroxyapatite (HA) ceramics were used to fabricate ceramic devices. Each group of devices consisted of three replicates. Ceramic and AZT mixtures were compressed at a load of 3000 lbs in a 10 mm diameter die using a hydraulic press. For in vitro studies, vitamin E oil was incorporated in six different ratios in devices containing HA (500 mg) and AZT (250 mg). Each device was suspended in phosphate buffered saline (pH 7.4). Devices containing oil released AZT in significantly lower amounts than devices containing no oil. In vivo studies were conducted with devices composed of homogeneous mixtures of 250 mg AZT and 500 mg TCP with and without vitamin E oil in the following combinations: AZT and TCP (Group I), Oil saturated TCP and AZT (Group II), and AZT pellet inserted in an oil saturated TCP shell (Group III). These devices were implanted subcutaneously in Sprague Dawley rats for two weeks. Group II and III devices delivered AZT at a significantly lower rate than Group I devices. Results of both studies suggest that treatment of ceramic devices with oil decreases the release rate and prolongs the delivery of AZT.