Synthesis of antibiotic-loaded hydroxyapatite beads and in vitro drug release testing

Various forms of hydroxyapatite (HAP) materials have been developed for use as bone grafts. Since the risk of local infection is associated with surgery, it seems reasonable to incorporate drugs such as antibiotics into implant materials. We therefore investigated the characteristics of drug incorporation into a spherical porous HAP bead (diameter = 8.48 mm, bulk porosity = 0.439) and its in vitro release behavior. Cefotiam (CTM) was used as a model antibiotic. Because of nonuniform pore distribution in the bead, distribution of CTM was estimated from the amounts of CTM experimentally determined at three different sites: the surface, halfway to the center, and the center of the beads. The results indicated that 90% of the drug was incorporated in the concentric outer 0.387 (radius = 1) section of the bead. CTM was released with a short lag time when the dry HAP bead was placed in water. Incorporation of CTM with egg phosphatidylcholine eliminated initial lag time and decreased the release rate of the drug from the bead. The lipid load was useful in controlling the release of CTM from the beads. In addition, to protect relatively unstable drugs from humidity and avoid contamination of drug-incorporated HAP beads an apparatus was designed with which the beads could be enclosed in vials in vacuo and under aseptic conditions on a bench-scale basis.