A NOVEL SKELETAL DRUG-DELIVERY SYSTEM USING A SELF-SETTING CALCIUM-PHOSPHATE CEMENT .5. DRUG-RELEASE BEHAVIOR FROM A HETEROGENEOUS DRUG-LOADED CEMENT CONTAINING AN ANTICANCER DRUG

A novel drug delivery device based on a self-setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium pho sphate has been developed and tested in vitro using the anticancer age nt 6-mercaptopurine (6-MP) as a model compound. X-ray diffraction resu lts suggest that equimolar mixtures of the calcium phosphate salts wer e transformed into hydroxyapatite after being mixed with a dilute phos phoric acid solution, even in the presence of various amounts of 6-MP powder. The inclusion of 6-MP in the reaction mixture resulted in the formation of a homogeneous drug-containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug -containing pellet. In vitro drug release from both the homogeneous an d heterogeneous drug-loaded cement pellets into simulated body fluid ( pH 7.25, 37.0 degrees C) was measured using the rotating-disk method. Release from the homogeneous 5% drug-loaded cements did not obey the H iguchi equation. The release rate from the heterogeneous drug-loaded c ements of different thicknesses (1, 2, and 3 mm) was a function of thi ckness, indicating that release kinetics could be controlled by the de sign of the cement formulation.