Bohner M, Lemaître J, Van Landuyt P, Zambelli P Y, Merkle H P, Gander B
ETH-Zürich, Pharmazie Abteilung, Switzerland.
J Pharm Sci. 1997 May;86(5):565-72. doi: 10.1021/js960405a.
A hydraulic calcium phosphate cement made of beta-tricalcium phosphate [beta-Ca3(PO4)2], monocalcium phosphate monohydrate [Ca(H2PO4)2-H2O], and water was used as a delivery system for the antibiotic gentamicin sulfate (GS). GS, added as powder or as aqueous solution, was very beneficial to the physicochemical properties of the cement. The setting time increased from 2 to 4.5 min with 3% (w/w) GS and then slowly decreased to 3.75 min with 16% (w/w) GS. The tensile strength increased from 0.4 to 1.6 MPa with 16% (w/w) GS. These effects were attributed to the presence of sulfate ions in GS. The release of GS from the cement was measured in a pH 7.4 phosphate-buffered saline solution at 37 degrees C by USP paddle method. Factors such as cement porosity, GS content and presence of sulfate ions or polymeric additives were investigated. The amount of GS released was roughly proportional to the square root of time up to approximately 50% release. Afterwards, the release rate markedly slowed down to zero. In all but two cement formulations, the total dose of GS was released within 7 days, indicating that no irreversible binding occurred between the cement paste and the antibiotic. When small amounts of hydroxypropylcellulose or poly(acrylic acid) were added to the cement, the maximum fraction released was a few percent lower than the total GS dose, suggesting some binding between the polymer and GS. The GS release rate was strongly influenced by the presence of sulfate ions in the cement paste and by the cement porosity. The higher the sulfate ion content of the cement paste, the lowe the GS release rate. This influence was attributed to the finer cement micro-structure induced by the presence of sulfate ions. Furthermore, when the initial cement porosity was increased from 38 to 69%, the release rate almost tripled (0.16 to 0.45 h-1/2). Finally, the biological activity of GS in the cement was maintained, as measured by assaying the release medium.
一种由β-磷酸三钙[β-Ca3(PO4)2]、一水磷酸二氢钙[Ca(H2PO4)2·H2O]和水制成的水硬性磷酸钙骨水泥被用作硫酸庆大霉素（GS）的给药系统。以粉末或水溶液形式添加的GS对骨水泥的物理化学性质非常有益。添加3%（w/w）GS时，凝固时间从2分钟增加到4.5分钟，然后随着16%（w/w）GS的添加，凝固时间缓慢降至3.75分钟。添加16%（w/w）GS时，拉伸强度从0.4 MPa增加到1.6 MPa。这些影响归因于GS中硫酸根离子的存在。通过美国药典桨法在37℃的pH 7.4磷酸盐缓冲盐溶液中测量GS从骨水泥中的释放。研究了骨水泥孔隙率、GS含量以及硫酸根离子或聚合物添加剂的存在等因素。在释放约50%之前，GS的释放量大致与时间的平方根成正比。之后，释放速率明显减慢至零。除了两种骨水泥配方外，所有配方中GS的总剂量在7天内释放完毕，这表明骨水泥浆与抗生素之间未发生不可逆结合。当向骨水泥中添加少量羟丙基纤维素或聚丙烯酸时，最大释放分数比GS总剂量低几个百分点，这表明聚合物与GS之间存在一些结合。GS的释放速率受到骨水泥浆中硫酸根离子的存在以及骨水泥孔隙率的强烈影响。骨水泥浆中硫酸根离子含量越高，GS释放速率越低。这种影响归因于硫酸根离子的存在导致骨水泥微观结构更精细。此外，当初始骨水泥孔隙率从38%增加到69%时，释放速率几乎增加了两倍（从0.16到0.45 h-1/2）。最后，通过分析释放介质测量发现，骨水泥中GS的生物活性得以保持。
