Otsuka M, Nakahigashi Y, Matsuda Y, Fox J L, Higuchi W I, Sugiyama Y
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan.
J Control Release. 1998 Mar 31;52(3):281-9. doi: 10.1016/s0168-3659(97)00264-2.
The relationship between in vitro and in vivo indomethacin (IMC) release from a self-setting bioactive apatite cement and cement size were investigated. Differently sized apatite cements (total weight, 500 mg); either 64 of the small size (2 mm diameter x 2 mm thickness), sixteen of the medium size (4 mm x 2 mm) or one of the large size (15 mm x 2 mm) were obtained from cement bulk powder containing tetracalcium phosphate, dicalcium phosphate dihydrate and hydroxyapatite. In vitro IMC release from the 1, 2 and 5% drug-loaded apatite cement systems in simulated body fluid (SBF) (pH 7.25) at 37 degrees C increased with increasing concentrations of IMC and with decreasing geometrical size of the cement. The plots of in vitro IMC release per unit area against the square root of time increased with increasing IMC concentrations, but not with decreasing geometrical size of the cement. After subcutaneous (s.c.) implantation of differently sized 1% IMC-loaded cements in male Wistar rats, the plasma IMC concentration and the area under the curve increased with decreasing cement diameter. The in vivo IMC release profiles of the cement were deconvoluted from the plasma IMC profiles after s.c. administration of IMC solution. The plots of in vivo IMC release per unit area against the square root of time suggested that the initial release from all 1% drug-loaded cements was very rapid, slowed after one day, but continued for over two weeks. The relationship between the in vitro release in SBF and the in vivo release in rats of IMC-loaded cements was linear.
研究了自固化生物活性磷灰石骨水泥体外和体内吲哚美辛（IMC）释放与骨水泥尺寸之间的关系。从含有磷酸四钙、二水磷酸二钙和羟基磷灰石的骨水泥散装粉末中获得了不同尺寸的磷灰石骨水泥（总重量500mg）；小尺寸的64个（直径2mm×厚度2mm）、中尺寸的16个（4mm×2mm）或大尺寸的1个（15mm×2mm）。在37℃的模拟体液（SBF，pH7.25）中，1%、2%和5%载药磷灰石骨水泥体系的体外IMC释放随着IMC浓度的增加和骨水泥几何尺寸的减小而增加。单位面积体外IMC释放量对时间平方根的曲线随着IMC浓度的增加而增加，但不随骨水泥几何尺寸的减小而增加。将不同尺寸的1%载IMC骨水泥皮下植入雄性Wistar大鼠后，血浆IMC浓度和曲线下面积随着骨水泥直径的减小而增加。皮下注射IMC溶液后，从血浆IMC曲线反卷积得到骨水泥的体内IMC释放曲线。单位面积体内IMC释放量对时间平方根的曲线表明，所有1%载药骨水泥的初始释放非常迅速，一天后减慢，但持续超过两周。载IMC骨水泥在SBF中的体外释放与在大鼠体内的释放之间的关系为线性。
