A NOVEL SKELETAL DRUG-DELIVERY SYSTEM USING SELF-SETTING CALCIUM-PHOSPHATE CEMENT .2. PHYSICOCHEMICAL PROPERTIES AND DRUG-RELEASE RATE OF THE CEMENT-CONTAINING INDOMETHACIN

A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been de veloped and tested in vitro with indomethacin as a model drug. Equimol ar mixtures of the calcium phosphate powders containing 2 and 5% of in domethacin were transformed into a hydroxyapatite after being mixed wi th a dilute phosphoric acid solution. X-ray diffraction and differenti al scanning calorimetry results suggested that indomethacin transforme d into an amorphous form in the pores of the cement matrix as it harde ned. In vitro drug release from cement pellets into a 0.1 mol/L phosph ate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Releas e from 2 and 5% drug-loaded cements followed the Higuchi model equatio n. The drug release profiles of 5% drug-loaded cements with different thicknesses (0.5, 1.0, and 1.5 g) overlapped up to 90% drug release, i ndicating that the drug concentration gradient in the pore was indepen dent of the thickness of the cement as expected from the model equatio n.