A NOVEL SKELETAL DRUG-DELIVERY SYSTEM USING SELF-SETTING CALCIUM-PHOSPHATE CEMENT .4. EFFECTS OF THE MIXING SOLUTION VOLUME ON THE DRUG-RELEASE RATE OF HETEROGENEOUS ASPIRIN-LOADED CEMENT

The effect of the mixing solution volume was investigated on the in vi tro drug-release rate of a novel drug-delivery device based on a self- setting bioactive calcium phosphate cement containing aspirin as a mod el drug. Equlmolar mixtures of metastable calcium phosphate powders co ntaining various proportions (3-40 w/w %) of seed hydroxyapatite cryst als transformed into hydroxyapatite after being mixed with dilute phos phoric acid. The drug release from cement pellets in vitro into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C by the rotating dis k method continued for more than 1 week. The drug-release rate from th e cement increased with increasing volumes of mixing solution. The rel ationship between the liquid/powder ratio and the porosity of the ceme nt was a straight line, indicating that the cement porosity depended o n the amount of the mixing solution, but was independent of the amount of seed crystals. Drug release from the cement followed the modified Fick's law, with the rate increasing with the amount of mixing solutio n, since the porosity depended on the amount. The tortuosity of the ce ments was estimated from the modified Fick's equation, and the relatio nships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results sugge sted that the drug-release rates from the cement were controlled by th e drug diffusion in the pores.