布洛芬滴丸的成型工艺及体外溶出度研究
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摘要
目的:研究布洛芬滴丸的成型工艺并测定其体外溶出度。方法:在单因素试验的基础上,采用响应面法,以圆整度、载药率、丸重差异为评价指标,筛选成型工艺中的药物与基质质量比、药液温度、制冷温度;同时进行验证试验,考察最优工艺所制滴丸的体外溶出度并与市售片剂进行比较。结果:布洛芬滴丸的最优成型工艺为药物与基质质量比1∶6,药液温度83℃,制冷温度7.3℃。验证试验中自制滴丸的圆整度为0.945 9、载药率为99.82%、丸重差异为0.040 28,含药量约为30 mg/丸;综合评分的实际值为0.972 5,与理论值(0.980 0)的偏差值为0.771 2%,RSD<1.5%(n=3)。所制滴丸5 min溶出度为25.36%,30 min累积溶出度达到90.12%,与市售布洛芬片剂体外释药行为相似(f_2=54.91),符合一级药动学方程。结论:该成型工艺方法简单、稳定可行;以优化成型工艺所制滴丸可快速释药且重复性好。
OBJECTIVE:To study the formation technology of Ibuprofen dropping pills and determine the dissolution in vitro.METHODS:Based on single factor test and with the spherical degree,drug-loading rate and pill weight variation as the evaluated indexes,response surface methodology was employed to screen the ratios of drug to matrix,drug solution temperatures and cryogenic temperatures in the formation technology,and verification tests were conducted. The dissolution in vitro of the dropping pills prepared by the optimal technology was investigated and compared with that of the preparations sold in the market. RESULTS:The optimal formation technology of Ibuprofen dropping pills was as follows as the ratio of drug to matrix of 1 ∶ 6,drug solution temperature of 83 ℃ and cryogenic temperature of 7.3 ℃. In the verification tests,the self-made dropping pills demonstrated a spherical degree of 0.945 9,drug-loading rate of 99.82%,pill weight variation of 0.040 28 and drug-loading capacity of 30 mg/pill,with the actual comprehensive score of 0.972 5,deviating from the theoretical one(0.980 0)by 0.771 2%(RSD<1.5%,n=3). The dropping pills prepared had a dissolution rate of 25.36% at 5 min and an accumulated dissolution rate up to 90.12% at 30 min,similar with the Ibuprofen tablets sold in the market in drug release in vitro(f_2=54.91),conforming to a first-order kinetic equation.CONCLUSIONS:The optimized formation technology is simple,stable,feasible and well reproducible,and the dropping pills which are prepared by such technology can release drug quickly.
OBJECTIVE:To study the formation technology of Ibuprofen dropping pills and determine the dissolution in vitro.METHODS:Based on single factor test and with the spherical degree,drug-loading rate and pill weight variation as the evaluated indexes,response surface methodology was employed to screen the ratios of drug to matrix,drug solution temperatures and cryogenic temperatures in the formation technology,and verification tests were conducted. The dissolution in vitro of the dropping pills prepared by the optimal technology was investigated and compared with that of the preparations sold in the market. RESULTS:The optimal formation technology of Ibuprofen dropping pills was as follows as the ratio of drug to matrix of 1 ∶ 6,drug solution temperature of 83 ℃ and cryogenic temperature of 7.3 ℃. In the verification tests,the self-made dropping pills demonstrated a spherical degree of 0.945 9,drug-loading rate of 99.82%,pill weight variation of 0.040 28 and drug-loading capacity of 30 mg/pill,with the actual comprehensive score of 0.972 5,deviating from the theoretical one(0.980 0)by 0.771 2%(RSD<1.5%,n=3). The dropping pills prepared had a dissolution rate of 25.36% at 5 min and an accumulated dissolution rate up to 90.12% at 30 min,similar with the Ibuprofen tablets sold in the market in drug release in vitro(f_2=54.91),conforming to a first-order kinetic equation.CONCLUSIONS:The optimized formation technology is simple,stable,feasible and well reproducible,and the dropping pills which are prepared by such technology can release drug quickly.
引文
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[3]路长飞,马晶,田月洁,等.布洛芬口服制剂致视觉异常不良反应/不良事件64例分析[J].中国药房,2013,24(40):3 822.
[4]翁蓓,张岩.中药滴丸剂的研究进展[J].天津药学,2013,25(2):50.
[5]耿东升,兰建国,陈明.光纤药物溶出仪实时测定布洛芬片溶出度的研究[J].西北药学杂志,2009,24(5):394.
[6]祝侠丽,贾永艳,黄海英,等.正交设计法优化布洛芬缓释骨架片的处方工艺[J].中国药房,2014,25(9):830.
[7]彭婷婷,王卫华.高效液相色谱法测定布洛芬片中布洛芬的含量[J].齐齐哈尔医学院学报,2011,32(17):2 820.
[8]国家药典委员会.中华人民共和国药典:四部[S].2015年版.北京:中国医药科技出版社,2015:375、11-12、121-122.
[9]张艳,李永哲.响应面法及其在药学领域中的应用[J].吉林化工学院学报,2012,29(7):20.
[10]李莉,张赛,何强,等.响应面法在试验设计与优化中的应用[J].实验室研究与探索,2015,34(8):41.
[11]谢沐风.如何科学、客观地制订溶出度试验质量标准[J].中国医药工业杂志,2012,43(3):A23.
[12]李晓斌,陈振斌,杨旸,等.响应面分析法优化槐叶中黄酮类化合物的提取工艺[J].中国药房,2015,26(7):960.
[13]刘水英,李新生,党娅,等.响应面法优化紫山药花青苷提取工艺及其抗氧化活性[J].食品科学,2015,35(22):85.
[14]陈丹妮,秦昆明,陈林伟,等.响应面法优化五倍子总鞣质的提取工艺[J].中国实验方剂学杂志,2015,21(14):20.