响应面分析法优化当归超临界提取物结肠定位微丸的制备工艺研究
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摘要
采用离子交联法制备当归超临界提取物丸芯,以丸芯载药量和包封率为指标,对影响载药量和包封率的多个因素进行考察,并采用Box-Behnken试验设计和响应面分析法对载药丸芯的处方进行优化,然后进行包衣工艺研究。通过体外释放研究,优选当归超临界提取物结肠定位微丸的包衣工艺及处方并评价其结肠靶向性。确定最佳的丸芯制备工艺∶3%果胶,果胶与卵磷脂比为4∶1,果胶药物比为4∶5,4%的醋酸锌溶液为交联剂,混匀温度35℃,交联温度35℃,交联时间30 min;包衣工艺∶包衣材料为尤特奇FS30D,包衣材料1.5%的柠檬酸三乙酯和聚氧乙烯脱水山梨醇单油酸酯(吐温-80),包衣材料1.2%的单硬脂酸甘油酯,包衣增重15%。最优工艺制备的当归超临界提取物结肠定位微丸在人工胃液中2 h几乎无释放,人工小肠液中4 h释放小于20%,人工结肠液中6 h释放大于90%,说明制备的当归超临界提取物结肠定位微丸具有良好的结肠靶向性。
To prepare pellets of supercritical fluid extraction( SFE) of Angelica Sinensis Radix by using the ionic crosslinking method,and the drug loading and encapsulation efficiency were used as the index to investigate the multiple factors which may impact the drug loading and encapsulation efficiency. Box-Behnken design and response surface analysis method were then taken to optimize the prescription of pellets and study the coating technology. Through the study on the release of pellets in vitro,an optimal coating technology and prescription of colon-specific pellets of Angelica Sinensis Radix SFE were selected and their colon targeting was evaluated.The optimal preparation parameters of pellets were determined as follows: 3% pectin; 4∶ 1 for pectin / lecithin; 4∶ 5 for pectin / SFE of Angelica Sinensis Radix; 4% zinc acetate solution as crosslinking agent,blending temperature 35 ℃,crosslinking temperature 35 ℃,crosslinking time 30 min; coating technology: coating material Eudragit FS 30 D,1. 5% triethyl citrate and polyoxyethylene sorbitan monooleate( tween-80),1. 2% monostearin and 15% coating weight gained. The colon-specific pellets of Angelica Sinensis Radix SFE prepared with optimized conditions were almost not released in simulated gastric fluid in 2 h,released less than 20% in simulated intestine fluid in 4 h,and released more than 90% in simulated colon fluid in 6 h,indicating that the colon-specific pellets of Angelica Sinensis Radix SFE had an excellent colon targeting property.
To prepare pellets of supercritical fluid extraction( SFE) of Angelica Sinensis Radix by using the ionic crosslinking method,and the drug loading and encapsulation efficiency were used as the index to investigate the multiple factors which may impact the drug loading and encapsulation efficiency. Box-Behnken design and response surface analysis method were then taken to optimize the prescription of pellets and study the coating technology. Through the study on the release of pellets in vitro,an optimal coating technology and prescription of colon-specific pellets of Angelica Sinensis Radix SFE were selected and their colon targeting was evaluated.The optimal preparation parameters of pellets were determined as follows: 3% pectin; 4∶ 1 for pectin / lecithin; 4∶ 5 for pectin / SFE of Angelica Sinensis Radix; 4% zinc acetate solution as crosslinking agent,blending temperature 35 ℃,crosslinking temperature 35 ℃,crosslinking time 30 min; coating technology: coating material Eudragit FS 30 D,1. 5% triethyl citrate and polyoxyethylene sorbitan monooleate( tween-80),1. 2% monostearin and 15% coating weight gained. The colon-specific pellets of Angelica Sinensis Radix SFE prepared with optimized conditions were almost not released in simulated gastric fluid in 2 h,released less than 20% in simulated intestine fluid in 4 h,and released more than 90% in simulated colon fluid in 6 h,indicating that the colon-specific pellets of Angelica Sinensis Radix SFE had an excellent colon targeting property.
引文
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[2]钟小明,陈旭东,余鸿.当归药理作用的研究进展[J].四川解剖学杂志,2007,15(1):44.
[3]刘医辉,杨世英,马伟林,等.当归药理作用的研究进展[J].中国当代医药,2014,21(22):192.
[4]李晓宁,杨银花,赵博琛,等.超临界CO2流体技术萃取当归挥发油的工艺优选[J].中国实验方剂学杂志,2013,19(14):27.
[5]安静.当归提取物中不同组分配伍的协同抗炎、抗氧化作用研究[D].北京:北京中医药大学,2014.
[6]安静,李晓宁,赵博琛,等.当归超临界提取物对AOM/DSS诱导的小鼠炎症相关性结直肠癌的化学预防作用[J].中国中药杂志,2014,39(7):1265.
[7]赵博琛.当归有效组分配伍应用的结直肠癌化学预防效果评价及机理研究[D].北京:北京中医药大学,2015.
[8]朱盛山,梁文权,吕万良,等.药剂新剂型[M].北京:化学工业出版社,2003.
[9]赵远航,盛林杰,谌晨,等.卵磷脂/果胶钙凝胶球的制备及性能研究[J].中国新药杂志,2015,24(6):713
[10]潘昕,黄莹,朱春娥,等.混合膜材及添加剂对包衣膜性质的影响[J].中国现代应用药学,2013,30(6):619.