替硝唑3种阴道给药剂型的释放及特殊安全性研究

发布时间：2018-03-15 19:40

  本文选题：替硝唑　切入点：缓释栓剂　出处：《毒理学杂志》2017年01期 　论文类型：期刊论文

【摘要】：目的比较研究替硝唑长效缓释栓剂、阴道凝胶剂和阴道缓释片3种剂型的释放度、释放机制及特殊毒性。研究三者的溶出曲线、释药机制及缓释效果。方法将自制片剂、自制凝胶剂和市售栓剂分别做体外溶出试验,绘制相应的溶出曲线,研究释放机制。皮肤过敏性试验:取豚鼠12只,随机分成4组,分别涂抹3种剂型药物及阳性对照药,重复给药诱导,观察有无过敏反应。家兔阴道刺激性试验:取雌兔12只,随机分为4组,其中3组为给药组,1组为空白对照组。将药物推入大耳白兔阴道5cm,观察现象。隔天给药1次,连续7次,观察动物情况。随后处死动物,摘取生殖器官,对其进行刺激性性评价,做成切片进行病理学检查。结果栓剂符合Higuchi方程,为扩散与溶胀双重机制,且以扩散为主;凝胶剂符合Higuchi方程,为扩散与骨架溶蚀双重机制,且以扩散为主;片剂符合零级释药模型,为扩散与骨架溶蚀双重机制,且以骨架溶蚀为主。片剂零级释放,释放更均匀。结论释药效果比较研究发现,缓释效果片剂优于其他二者,缓释片剂的释放更均匀。刺激性过敏性试验结果表明3种剂型均无刺激致敏性,安全可靠。
[Abstract]:Objective to compare the release rate, release mechanism and special toxicity of tinidazole long-acting sustained-release suppository, vaginal gel and vaginal sustained-release tablet. Self-made gel and commercial suppository were used for dissolution test in vitro, corresponding dissolution curve was drawn, and release mechanism was studied. Skin anaphylactic test: 12 guinea pigs were randomly divided into 4 groups, 3 dosage forms and 3 positive control drugs were smeared respectively. The vaginal irritation test: 12 female rabbits were randomly divided into 4 groups. Three of them were treated as blank control group. The drug was pushed into the vagina of rabbits with big ears for 5 cm to observe the phenomenon. Once every other day, 7 times in succession, the animals were observed. Then the animals were killed and their reproductive organs were removed. The results showed that the suppository accords with Higuchi equation, which is the double mechanism of diffusion and swelling, and is mainly diffusive, and the gel conforms to Higuchi equation, which is the double mechanism of diffusion and skeleton dissolution. The tablets accord with the zero-order drug release model, which is the dual mechanism of diffusion and skeleton dissolution, and the skeleton dissolution is the main mechanism. The release of sustained-release tablets was more uniform than that of other two tablets. The results of irritation allergic test showed that all the three formulations had no irritation sensitization and were safe and reliable.
【作者单位】： 辽宁大学药学院;辽宁省生物大分子计算模拟与信息处理工程技术研究中心;
【基金】：辽宁省教育厅高等学校创新团队项目(项目编号:LT2015011)
【分类号】：R965
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本文编号：1616522