替硝唑原位固化缓释注射剂的制备与体内外性质考察

制备了一种原位固化缓释注射剂,在牙周病变部位缓释药物达7 d,并对其体外性质及体内药动学进行考察。制备原位固化缓释注射剂,考察该注射剂的固化时间;利用扫描电镜对该注射剂固化后的表面形态进行了表征;测定0℃、25℃、37℃下凝胶剪切力随剪切率变化的曲线,绘制流变学曲线,并考察温度对黏度的影响;考察体外释放行为,并对其进行拟合;建立家兔牙周炎模型,考察其体内药动学。该注射剂稳定性良好,不易分层、分解,遇水后在6 s左右固化,可以黏附于牙周袋内,不易脱落;固化后,表面形成较多小孔,为药物扩散通道;在25℃、37℃下均为典型的牛顿流体,室温下通针性良好,使用方便;体外释放行为符合Korsmeyer-Peppas释放动力学方程,释放平缓,突释小,可持续7 d,能达到良好的缓释作用;药动学实验结果与各项参数的拟合结果表明了替硝唑原位固化缓释注射剂在体内缓释性能良好,制剂组可用一室模型进行很好的拟合,可维持牙龈沟液(GCF)内有效治疗浓度长达168 h,满足牙周炎临床治疗需要,该替硝唑原位注射缓释注射剂具有较好的应用前景。

Preparation and in vitro and in vivo study on tinidazole in situ forming sustained-release injection

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.