【作者】 周健鹏；

【导师】 张韻慧；

【作者基本信息】 天津大学 ， 药物分析学， 2010， 硕士

【摘要】 本论文建立了高效液相色谱法测定吲哚美辛贴片的含量和有关物质。采用碟上桨法测定贴片的体外释放度,并利用SPSS软件估算相应的体外释放参数,确定药物体外释放特征。在此基础上,通过体内药动学参数计算,进一步研究了吲哚美辛贴片的体内外相关性。1.高效液相色谱法测定吲哚美辛贴片含量和有关物质方法的研究色谱条件:C18柱（150 mm×4.6 mm ID,5μm）,以甲醇∶水∶磷酸（600∶400∶1,v/v/v）为流动相,流速:1.0 mL·min^-1,柱温:40℃,检测波长为228 nm。吲哚美辛的线性范围分别为10～200μg·mL^-1和0.5～10μg·mL^-1,最低可定量限为0.5 ng,平均回收率为99.6%,精密度良好,适用于吲哚美辛贴片含量及有关物质的测定。2.吲哚美辛贴片体外释放度及体内外相关性研究采用碟上桨装置,水900 ml为溶出介质,转速为每分钟100转,色谱条件同含量测定项下。吲哚美辛的线性范围为1.0～20μg·mL^-1,平均回收率为99.5%。利用SPSS软件拟合体外释放数据,选取多个模型进行计算,结果符合一级速率方程,R²值为0.9268。将体外释放数据带入方程,计算T50、Td等释放参数,结果满意。通过测定大鼠血药浓度,计算主要药动学参数,房室模型为一室模型一级吸收,R²值为0.9832,采用Wagner-Nelson法计算各时间点体内药物累积吸收百分数,以24h内体内药物累积吸收百分率（Fa）为因变量,以对应体外累积溶出百分率（Fd）为自变量,进行回归。测定结果的回归方程及回归系数通过显著性检验（P <0.01）,表明Fa与Fd具有显著相关性。更多还原

【Abstract】 To establish a method to determine the content and related substances of indomethacin patch by HPLC. The trap-paddle method was used to determine the dissolution of patch. We used the SPSS software to calculate the dissolution parameter and studied the character of vitro dissolution. Then research on the correlation between dissolution rate in vitro and absorption rate in vivo was continued by calculating the pharmacokinetic parameter.Section one: the research on the determination of indomethacin patch’s content and related substances.Liquid chromatography was performed on a C18 column（150×4.6 mm,5μm）, the mobile phase consisted of methanol, water and phosphoric acid （600:400:1,v/v/v）, used a flow rate of 1.0 mL·min^-1 at 40℃column temperature, and the detection wavelength was 228 nm. The linear concentration ranges of indomethacin were 10～200μg·mL^-1 and 0.5～10μg·mL^-1, respectively. The lower limit of quantification of indomethacin was 0.5 ng and the average recovery was 99.6%. The method precision was good and the method could be used for determining the content and the related substances of indomethacin patch.Section two: the research on the vitro dissolution and the correlation between dissolution rate in vitro and absorption rate in vivo. We used the trap-paddle apparatus, and 900 ml water as the sovent with a rotation speed of 100 rpm, the assay’s chromatographic condition was used. The linear concentration ranges of indomethacin was 1.0～20μg·mL^-1, and the average recovery was 99.5%. The SPSS software was used to fit dissolution data with several models. The results was consistent with first lever equation, and the R2 was 0.9268. Then calculated the dissolution parameters （T50, Td）, the results was satisfaction. At last, we determined the indomethacin concentration in rat skin and calculated main pharmacokinetic parameters which as follows: Compartment number=1, Weight=1, R2=0.9832. Calculated the Fraction absorption at different times with the Wagner-Nelson method. There was a significant relationship between absorption in vivo and dissolution in vitro （P<0.01）.更多还原