磷酸川芎嗪pH敏感胃漂浮水凝胶的制备及释放度研究
|
摘要
目的以磷酸川芎嗪为模型药物,制备pH敏感胃漂浮水凝胶,考察其体外释放度。方法以黄原胶、魔芋胶和PEG-2 000为原料,水浴温度为50℃下制备磷酸川芎嗪胃漂浮水凝胶;以人工胃液为溶出介质,转速为150r·min~(-1),在不同时间取样,HPLC法测定pH敏感胃漂浮水凝胶中磷酸川芎嗪的含量,计算累积释放百分率。结果磷酸川芎嗪质量浓度在2～200.0μg·mL~(-1)范围内与峰面积线性关系良好:y=39 781.11x+5 132.48,r=0.999 9,平均回收率为99.36%,RSD值为0.19%。磷酸川芎嗪pH敏感胃漂浮水凝胶可持续释放12h,释放率达85%以上。结论该方法简单、可靠、重复性好,可用于磷酸川芎嗪pH敏感胃漂浮水凝胶的制备。
Objective To prepare pH-sensitive floating hydrogels for ligustrazine phosphate,and to investigate the drug release characteristics of pH sensitive floating hydrogels for ligustrazine phosphate.Methods Ligustrazine phosphate pH sensitive floating hydrogels were prepared at 50℃ based on xanthan gum,konjac gum and PEG-2 000;by employing the simulated gastric fluid,at 150 r·min~(-1),the content of ligustrazine phosphate was determined by HPLC method.The drug release of pH-sensitive floating hydrogels in vitro was calculated.Results The linear range of ligustrazine phosphate was 2-200.0μg·mL~(-1),and the linear equation was y=39 781.11 x+5 132.48,r=0.999 9.From pH-sensitive floating hydrogels,ligustrazine phosphate was released over a period of 12 h,and the maximum release of ligustrazine phosphate reached more than 85%;the average recovery was 99.36%,and the RSD was 0.19%.Conclusion Because the preparation process is simple,accurate,and reproducible,it could be used for preparing ligustrazine phosphate pH sensitive floating hydrogels.
Objective To prepare pH-sensitive floating hydrogels for ligustrazine phosphate,and to investigate the drug release characteristics of pH sensitive floating hydrogels for ligustrazine phosphate.Methods Ligustrazine phosphate pH sensitive floating hydrogels were prepared at 50℃ based on xanthan gum,konjac gum and PEG-2 000;by employing the simulated gastric fluid,at 150 r·min~(-1),the content of ligustrazine phosphate was determined by HPLC method.The drug release of pH-sensitive floating hydrogels in vitro was calculated.Results The linear range of ligustrazine phosphate was 2-200.0μg·mL~(-1),and the linear equation was y=39 781.11 x+5 132.48,r=0.999 9.From pH-sensitive floating hydrogels,ligustrazine phosphate was released over a period of 12 h,and the maximum release of ligustrazine phosphate reached more than 85%;the average recovery was 99.36%,and the RSD was 0.19%.Conclusion Because the preparation process is simple,accurate,and reproducible,it could be used for preparing ligustrazine phosphate pH sensitive floating hydrogels.
引文
[1]国家药典委员会.中国药典:2015年版:二部[S].北京:中国医药科技出版社,2015:1563.
[2]肖衍宇,陈志鹏,刘雯,等.磷酸川芎嗪缓释制剂在比格犬体内的药动学和生物等效性研究[J].中国药学杂志,2011,46(17):1344-1348.
[3]汉会勋,马云淑,崔利利,等.磷酸川芎嗪透皮贴剂制备及辛夷挥发油促渗作用考察[J].中国药学杂志,2011,46(24):1915-1918.
[4]叶勇,周莉玲,晏亦琳,等.微透析法研究磷酸川芎嗪体外血浆蛋白结合率[J].中国药学杂志,2009,44(20):1567-1570.
[5]肖衍宇,陈志鹏,平其能,等.磷酸川芎嗪理化性质及生物学性质的考察[J].中国医院药学杂志,2009,29(21):1810-1814.
[6]刘立群,崔晓兰,曲韵智.磷酸川芎嗪制剂研究概况[J].北方药学,2013,10(1):40-41,18.
[7]晏菲,马云淑,张惠玲.草果挥发油作促渗剂的磷酸川芎嗪贴剂对大鼠心肌缺血的影响[J].华西药学杂志,2017,32(4):378-380.
[8]周惠芬,何昱,张宇燕,等.川芎和黄芪有效部位组合给药后川芎嗪在脑缺血再灌注大鼠体内的PK-PD结合研究[J].中草药,2016,47(19):3463-3468.
[9]尹大伟,周英,刘玉婷,等.水凝胶的最新研究进展[J].化工新型材料,2012,40(2):21-24.
[10]张滢,刘梁,王庭宏,等.pH敏感纳米凝胶的制备及其在siRNA转染中的应用[J].高分子学报,2017,(7):1150-1158.
[11]张莉,王蛘,高会乐,等.穿膜肽R8和pH敏感型可断裂PEG共修饰脂质体的构建[J].药学学报,2015,50(6):760-766.
[12]王丽.压制包衣法制备磷酸川芎嗪脉冲释放片的研究[D].哈尔滨:黑龙江中医药大学,2015:10-26.
[13]安佃云,贺亚静,张建芳,等.磷酸川芎嗪透皮贴含量均匀度及释放度测定[J].药物分析杂志,2014,34(11):2087-2090.
[14]郑少华,李欣,周莉,等.姜黄素缓释片的制备及释放度研究[J].西北药学杂志,2015,30(1):65-67.
[15]宋志刚,张向阳.黄原胶在医药领域研究进展[J].济宁医学院学报,2016,39(4):229-233.
[16]Mikac U,Sepe A,Baumgartner S,et al.The influence of high drug loading in xanthan tablets and media with different physiological pH and ionic strength on swelling and release[J].Mol Pharm,2016,13(3):1147-1157.
[17]Maiti S,Mukherjee S.Controlled drug delivery attributes of co-polymer micelles and xanthan-O-carboxymethyl hydrogel particles[J].Int J Biol Macromol,2014,70:37-43.
[18]叶婷.魔芋胶基胃漂浮控释系统的构建与调控[D].武汉:华中农业大学,2014:38-39.
[19]张瑜,田会婷,朱晔.乙醇对魔芋胶骨架片体外药物释放的影响[J].河南大学学报:医学版,2017,36(4):265-268.
[20]朱慧,吴伟都,潘永明,等.黄原胶与阴离子瓜尔胶复配溶液的流变特性研究[J].中国食品学报,2014,14(5):55-61.
[21]李岩,孙婷,赵欣,等.复方骆驼蓬子水凝胶贴剂处方工艺研究[J].西北药学杂志,2016,31(2):176-180.
[2]肖衍宇,陈志鹏,刘雯,等.磷酸川芎嗪缓释制剂在比格犬体内的药动学和生物等效性研究[J].中国药学杂志,2011,46(17):1344-1348.
[3]汉会勋,马云淑,崔利利,等.磷酸川芎嗪透皮贴剂制备及辛夷挥发油促渗作用考察[J].中国药学杂志,2011,46(24):1915-1918.
[4]叶勇,周莉玲,晏亦琳,等.微透析法研究磷酸川芎嗪体外血浆蛋白结合率[J].中国药学杂志,2009,44(20):1567-1570.
[5]肖衍宇,陈志鹏,平其能,等.磷酸川芎嗪理化性质及生物学性质的考察[J].中国医院药学杂志,2009,29(21):1810-1814.
[6]刘立群,崔晓兰,曲韵智.磷酸川芎嗪制剂研究概况[J].北方药学,2013,10(1):40-41,18.
[7]晏菲,马云淑,张惠玲.草果挥发油作促渗剂的磷酸川芎嗪贴剂对大鼠心肌缺血的影响[J].华西药学杂志,2017,32(4):378-380.
[8]周惠芬,何昱,张宇燕,等.川芎和黄芪有效部位组合给药后川芎嗪在脑缺血再灌注大鼠体内的PK-PD结合研究[J].中草药,2016,47(19):3463-3468.
[9]尹大伟,周英,刘玉婷,等.水凝胶的最新研究进展[J].化工新型材料,2012,40(2):21-24.
[10]张滢,刘梁,王庭宏,等.pH敏感纳米凝胶的制备及其在siRNA转染中的应用[J].高分子学报,2017,(7):1150-1158.
[11]张莉,王蛘,高会乐,等.穿膜肽R8和pH敏感型可断裂PEG共修饰脂质体的构建[J].药学学报,2015,50(6):760-766.
[12]王丽.压制包衣法制备磷酸川芎嗪脉冲释放片的研究[D].哈尔滨:黑龙江中医药大学,2015:10-26.
[13]安佃云,贺亚静,张建芳,等.磷酸川芎嗪透皮贴含量均匀度及释放度测定[J].药物分析杂志,2014,34(11):2087-2090.
[14]郑少华,李欣,周莉,等.姜黄素缓释片的制备及释放度研究[J].西北药学杂志,2015,30(1):65-67.
[15]宋志刚,张向阳.黄原胶在医药领域研究进展[J].济宁医学院学报,2016,39(4):229-233.
[16]Mikac U,Sepe A,Baumgartner S,et al.The influence of high drug loading in xanthan tablets and media with different physiological pH and ionic strength on swelling and release[J].Mol Pharm,2016,13(3):1147-1157.
[17]Maiti S,Mukherjee S.Controlled drug delivery attributes of co-polymer micelles and xanthan-O-carboxymethyl hydrogel particles[J].Int J Biol Macromol,2014,70:37-43.
[18]叶婷.魔芋胶基胃漂浮控释系统的构建与调控[D].武汉:华中农业大学,2014:38-39.
[19]张瑜,田会婷,朱晔.乙醇对魔芋胶骨架片体外药物释放的影响[J].河南大学学报:医学版,2017,36(4):265-268.
[20]朱慧,吴伟都,潘永明,等.黄原胶与阴离子瓜尔胶复配溶液的流变特性研究[J].中国食品学报,2014,14(5):55-61.
[21]李岩,孙婷,赵欣,等.复方骆驼蓬子水凝胶贴剂处方工艺研究[J].西北药学杂志,2016,31(2):176-180.