天麻素温敏型鼻用原位凝胶的制备研究
|
摘要
以天麻素为主药,泊洛沙姆P407和P188为凝胶材料制备凝胶,考察P407、P188的浓度及药物的加入对胶凝温度和体系黏度的影响,优化处方组成;采用无膜溶出法,扩散池法和透析袋法考察凝胶的体外释药行为。确定天麻素含量为10%,以P407 20%,P188 1. 5%或2%为优化的处方组成,平均凝胶温度分别为31. 5℃和33. 6℃。体外释放结果显示三种方法药物均释放完全,无膜溶出法显示药物的释放量与溶蚀量具有良好的相关性;透析袋法表明药物以扩散和溶蚀相结合的方式释药,且以扩散方式为主。天麻素原位凝胶制备工艺简单,药物释放具有缓释行为,适合鼻腔给药。
Gastrodin nasal in situ gel was prepared with poloxamer 407 and poloxamer 188 as the matrices. Effects of concentrations of P407 and P188 and the addition of drugs on gelation temperature and viscosity of the system were investigated by single factor test. Three methods including membrane-free,Franz diffusion cell and dialysis cell were used separately to study the in vitro drug release characteristics. The content of gastrodin was fixed as 10%,and the optimized formulations were composed of 20% P407 and 1. 5% or 2% P188. The average gel temperatures were 31. 5 ℃ and 33. 6 ℃,respectively. The drug was completely released,and a good correlation between drug release amount and erosion rate of the gel was obtained in membrane-free method. The drug released by the combination of diffusion and erosion in dialysis cell method,and it was consistent with the Higuchi equation. The gastrodin nasal in situ gel with prolonged drug release was simple to prepare and was suitable for nasal administration.
Gastrodin nasal in situ gel was prepared with poloxamer 407 and poloxamer 188 as the matrices. Effects of concentrations of P407 and P188 and the addition of drugs on gelation temperature and viscosity of the system were investigated by single factor test. Three methods including membrane-free,Franz diffusion cell and dialysis cell were used separately to study the in vitro drug release characteristics. The content of gastrodin was fixed as 10%,and the optimized formulations were composed of 20% P407 and 1. 5% or 2% P188. The average gel temperatures were 31. 5 ℃ and 33. 6 ℃,respectively. The drug was completely released,and a good correlation between drug release amount and erosion rate of the gel was obtained in membrane-free method. The drug released by the combination of diffusion and erosion in dialysis cell method,and it was consistent with the Higuchi equation. The gastrodin nasal in situ gel with prolonged drug release was simple to prepare and was suitable for nasal administration.
引文
[1]龚其海,石京山,杨丹莉,等.天麻素在中枢神经系统的药理作用及其机制[J].中国新药与临床杂志,2011,30(3):176-179.
[2]刘智慧,马浩,王伟平,等.天麻素及派立辛改善东莨菪碱致学习记忆障碍的构效关系[J].药学学报,2016,51(5):743-748.
[3]章正祥,曹克刚,范吉平.天麻素对多巴胺、硝酸甘油诱发的血管舒缩异常模型大鼠血流调节作用[J].中华中医药杂志,2012,27(11):2959-2962.
[4]游金辉,谭天秩,匡安仁,等.3H-天麻苷元和3H-天麻素在小鼠体内的分布和代谢[J].华西医科大学学报,1994,25(3):325-328.
[5] MANDA P,HARGETT J K,VAKA S R,et al. Delivery of cefotaxime to the brain via intranasal administration[J]. Drug Dev Ind Pharm,2011,37(11):1306-1310.
[6] RUAN Yeping,YAO Li,ZHANG Bingbing,et al. Nanoparticlemediateddelivery of eurotoxin-II to the brain with intranasal administration:an effective strategy to improve antinociceptive activity of neurotoxin[J]. Drug Dev Ind Pharm,2012,38(1):123-128.
[7]陶涛,赵雁,岳鹏,等.石杉碱甲鼻用原位凝胶的制备及其经鼻脑靶向性评价[J].药学学报,2006,41(11):1104-1110.
[8]宋晓玲,石森林.鼻黏膜生物黏附给药系统的研究进展[J].中国医药工业杂志,2009,40(1):59-62.
[9]魏培,邓树海,李凌冰,等.原位凝胶缓释给药系统的研究进展[J].中国医药工业杂志,2007,38(12):890-894.
[10]谢悦良,范景辉,丁劲松,等.川陈皮素温敏型鼻用原位凝胶体外释药行为研究[J].中国医药工业杂志,2011,42(3):189-192.
[11]卢浩扬,林媛媛,车俊秀,等.星点设计-效应面法优化芷芎散温敏凝胶的处方及其鼻黏膜渗透特性研究[J].中草药,2014,45(13):1845-1849.
[2]刘智慧,马浩,王伟平,等.天麻素及派立辛改善东莨菪碱致学习记忆障碍的构效关系[J].药学学报,2016,51(5):743-748.
[3]章正祥,曹克刚,范吉平.天麻素对多巴胺、硝酸甘油诱发的血管舒缩异常模型大鼠血流调节作用[J].中华中医药杂志,2012,27(11):2959-2962.
[4]游金辉,谭天秩,匡安仁,等.3H-天麻苷元和3H-天麻素在小鼠体内的分布和代谢[J].华西医科大学学报,1994,25(3):325-328.
[5] MANDA P,HARGETT J K,VAKA S R,et al. Delivery of cefotaxime to the brain via intranasal administration[J]. Drug Dev Ind Pharm,2011,37(11):1306-1310.
[6] RUAN Yeping,YAO Li,ZHANG Bingbing,et al. Nanoparticlemediateddelivery of eurotoxin-II to the brain with intranasal administration:an effective strategy to improve antinociceptive activity of neurotoxin[J]. Drug Dev Ind Pharm,2012,38(1):123-128.
[7]陶涛,赵雁,岳鹏,等.石杉碱甲鼻用原位凝胶的制备及其经鼻脑靶向性评价[J].药学学报,2006,41(11):1104-1110.
[8]宋晓玲,石森林.鼻黏膜生物黏附给药系统的研究进展[J].中国医药工业杂志,2009,40(1):59-62.
[9]魏培,邓树海,李凌冰,等.原位凝胶缓释给药系统的研究进展[J].中国医药工业杂志,2007,38(12):890-894.
[10]谢悦良,范景辉,丁劲松,等.川陈皮素温敏型鼻用原位凝胶体外释药行为研究[J].中国医药工业杂志,2011,42(3):189-192.
[11]卢浩扬,林媛媛,车俊秀,等.星点设计-效应面法优化芷芎散温敏凝胶的处方及其鼻黏膜渗透特性研究[J].中草药,2014,45(13):1845-1849.