Zhang Lin, Parsons Daniel L, Navarre Christine, Kompella Uday B
Hoffman-La Roche, Nutley, NJ, USA.
J Control Release. 2002 Dec 13;85(1-3):73-81. doi: 10.1016/s0168-3659(02)00273-0.
The objective of this study was to develop sustained release Poloxamer 407 (P407) gel formulations of ceftiofur for treating foot infections in cattle. The formulations contained 25-35% (w/v) P407 alone or with polyvinyl pyrrolidone (PVP), carboxy methylcellulose (CMC), or hydroxylpropyl methylcellulose (HPMC) as an additive. The in-vitro release profiles of ceftiofur from the P407 formulations and the gel dissolution profiles were obtained simultaneously. Ceftiofur release followed zero order kinetics and correlated well with the weight percentage of P407 dissolved, indicating that the overall rate of release of ceftiofur is controlled by dissolution of the P407. An increase in P407 content from 25 to 35% resulted in a decrease in the rate of ceftiofur release. However, it appears that other factors may have also affected the drug release rate. Inclusion of PVP, CMC, and HPMC in the gel decreased the rate of release of ceftiofur to some extent. A decrease in the temperatures of the release medium decreased the release rate of ceftiofur, but not the rate of gel dissolution. The pH of the release medium showed a very slight effect on the release of ceftiofur and did not affect gel dissolution due to the non-ionic nature of P407.
本研究的目的是开发头孢噻呋的泊洛沙姆407（P407）缓释凝胶制剂，用于治疗牛足部感染。这些制剂单独含有25 - 35%（w/v）的P407，或与聚乙烯吡咯烷酮（PVP）、羧甲基纤维素（CMC）或羟丙基甲基纤维素（HPMC）作为添加剂混合。同时获得了头孢噻呋从P407制剂中的体外释放曲线和凝胶溶解曲线。头孢噻呋的释放遵循零级动力学，并且与溶解的P407的重量百分比相关性良好，这表明头孢噻呋的总体释放速率受P407溶解的控制。P407含量从25%增加到35%导致头孢噻呋释放速率降低。然而，似乎其他因素也可能影响了药物释放速率。在凝胶中加入PVP、CMC和HPMC在一定程度上降低了头孢噻呋的释放速率。释放介质温度的降低降低了头孢噻呋的释放速率，但没有降低凝胶溶解速率。由于P407的非离子性质，释放介质的pH值对头孢噻呋的释放影响非常小，并且不影响凝胶溶解。
