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

Abstract

The effect of the mixing solution volume was investigated on the in vitro drug-release rate of a novel drug-delivery device based on a self-setting bioactive calcium phosphate cement containing aspirin as a model drug. Equimolar mixtures of metastable calcium phosphate powders containing various proportions (3-40 w/w %) of seed hydroxyapatite crystals transformed into hydroxyapatite after being mixed with dilute phosphoric 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 disk method continued for more than 1 week. The drug-release rate from the cement increased with increasing volumes of mixing solution. The relationship between the liquid/powder ratio and the porosity of the cement was a straight line, indicating that the cement porosity depended on 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 solution, since the porosity depended on the amount. The tortuosity of the cements was estimated from the modified Fick's equation, and the relationships between the drug release rate and the tortuosity of the pore in the drug-loaded cement in the plots were nonlinear. The results suggested that the drug-release rates from the cement were controlled by the drug diffusion in the pores.