Effect of sodium bicarbonate amount on in vitro indomethacin release from self-setting carbonated-apatite cement

In the present study, to develop a drug delivery system with higher bioactivity in hard tissues by using the self-setting bioactive carbonate apatite cement, we have investigated the effects of sodium bicarbonate content on the in vitro drug release from a self-setting bioactive carbonate apatite cement containing indomethacin (IMC).

The cement powder systems constituted an equimolar mixture of tetracalcium phosphate (Ca4(PO4)2O) and dicalcium phosphate dihydrate (CaHPO4.2H2O), hydroxyapatite (HAP, Ca10(PO4)6(OH)2) seed crystals and sodium bicarbonate. Two types of 2% IMC loaded-cements were prepared as follows, one containing 0% HAP seed crystal and 0-10% sodium bicarbonate, and the other containing 40% HAP seed crystal and 0-10% sodium bicarbonate. The drug release profiles from 2% IMC loaded-cements were measured in simulated body fluid at pH 7.25 and 37.0 degrees C.

The drug release profiles from the cement matrix systems with or without seed crystals were estimated using a moment analysis computer program. The mean drug release time (MDT) and the time required for 50% drug release of the cement containing 0 and 40% seed crystal decreased with an increase of sodium bicarbonate. Furthermore, after the drug release the total pore volume of the cement matrix, as measured by mercury porosimetry, increased with an increase of sodium bicarbonate.

MDT and T50's were a function of adding the amount of sodium bicarbonate. The results of the relationship between the micropore distribution, total volume of pores after drug release and drug release supported the hypothesis that the variation in drug release from the cements resulting from the addition of sodium bicarbonate was mainly due to an increase in the diffusion of the drug in the micropores of the cement by dissolution or erosion of the cement matrix.