Otsuka M, Matsuda Y, Suwa Y, Fox J L, Higuchi W I
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan.
J Pharm Sci. 1994 May;83(5):611-5. doi: 10.1002/jps.2600830502.
A novel drug delivery device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro with indomethacin as a model drug. Equimolar mixtures of the calcium phosphate powders containing 2 and 5% of indomethacin were transformed into a hydroxyapatite after being mixed with a dilute phosphoric acid solution. X-ray diffraction and differential scanning calorimetry results suggested that indomethacin transformed into an amorphous form in the pores of the cement matrix as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for > 3 weeks. Release from 2 and 5% drug-loaded cements followed the Higuchi model equation. 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, indicating that the drug concentration gradient in the pore was independent of the thickness of the cement as expected from the model equation.
一种基于由磷酸四钙和磷酸二钙形成的自固化生物活性骨水泥的新型给药装置已被研发出来，并以吲哚美辛作为模型药物进行了体外测试。含有2%和5%吲哚美辛的磷酸钙粉末等摩尔混合物在与稀磷酸溶液混合后转化为羟基磷灰石。X射线衍射和差示扫描量热法结果表明，吲哚美辛在骨水泥基质硬化时在孔隙中转化为无定形形式。在pH 7.40和37℃条件下，骨水泥微丸在0.1 mol/L磷酸盐缓冲液中的体外药物释放持续超过3周。2%和5%载药骨水泥的释放遵循Higuchi模型方程。不同厚度（0.5、1.0和1.5 g）的5%载药骨水泥的药物释放曲线在药物释放高达90%时重叠，表明孔隙中的药物浓度梯度与骨水泥厚度无关，正如模型方程所预期的那样。
