替硝唑原位固化缓释注射剂制备及稳定性研究  

Preparation and Stability Study on Tinidazole in Situ Forming Sustained-Release Injection

作　　者：许颖[1] 居敏俐[2] 沈雁[3] 涂家生[3] 

机构地区：[1]江苏大学药学院,江苏镇江212013 [2]上海医药工业研究院、上海呼吸系统药物工程技术研究中心,上海200437 [3]中国药科大学药剂学教研室,南京210009

出　　处：《中国药学杂志》2014年第7期567-571,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81202930);江苏省高校自然科学研究面上项目(12KJB350002);江苏大学高级人才科研启动基金(11JDG122)

摘　　要：目的对替硝唑原位固化缓释制剂处方进行优化,并对制剂灭菌工艺、稳定性、刺激性进行考察。方法制备替硝唑原位固化缓释制剂,以释放度为指标,进行单因素考察;以灭菌后制剂的外观、黏度等指标考察灭菌工艺;分别考察制剂在光照(4 500±500)lx及温度(25或40℃)条件下贮存10 d稳定性;观察给药后对大鼠口腔黏膜的刺激性。结果处方中加入4mg·mL-1甘油,制剂在体外可缓慢释放7 d;湿热灭菌121℃,8 min后,制剂的颜色基本不变,各项指标符合要求;光照及高温储存10 d后,制剂颜色明显加深,贮藏时应注意避光阴凉;给药7 d后,大鼠口腔黏膜无充血、肿胀现象,牙龈完好,血管略有扩张。结论替硝唑原位固化缓释制剂具有7 d缓释效果,稳定性好,刺激性小,具有良好的应用前景。OBJECTIVE To optimize the formulation of tinidazole in situ forming sustained-release injection, and investigate its sterilization, stability and irritation. METHODS Single factor test was performed to optimize the preparation process of tinidazole in situ forming sustained-release injection with drug release as the index. Sterilization was inspected with the index of appearance, viscosi- ty and so on. The formulation stability under light （4 500 ±500） lx and high temperature （25 or 40 ℃） was investigated respectively. Irritation of the injection for rat oral mucosa was observed. RESULTS Tinidazole was smoothly released for 7 d from the formulation containing 4 mg . mL-1 glycerol. The appearance, viscosity and other indexes of the injection were qualified after sterilization at 121 ℃ for 8 min. The injection should be kept away from light and high temperature for its color turned deeper in these situations. There were no engorgement and swollen on oral mucosa 7 d after administration, however mild angiectasis was observed. CONCLUSION Tinidazole in situ forming sustained-release injection had 7 d long-lasting effect and good stability, and there was no significant irritation effect. These results indicate that this injection is safe, valuable and has good development prospects.

关 键 词：替硝唑 缓释 原位固化 灭菌 稳定性 刺激性 

分 类 号：R944[医药卫生—药剂学]