相似因子法评价复方对乙酰氨基酚片主药成分的体外溶出度

Research of the invitro dissolution of main ingredient in compound paracetamol tablets by similar factor method

目的建立复方对乙酰氨基酚片中对乙酰氨基酚、阿司匹林、咖啡因3个组分的含量测定方法,并应用此方法观察3种组分的体外溶出差异。方法采用高效液相色谱法,使用Agilent C18色谱柱,以甲醇—磷酸二氢钾(0.05mol/L)—三乙胺(25:75:0.02,用磷酸调节pH值至3.4)为流动相,流速为1.0ml/min,检测波长为272nm,柱温为30℃。溶出度采用转篮法,以盐酸溶液(稀盐酸24ml加水稀释)1000ml溶出介质,转速为100r/min,温度为(37±0.5)℃,分别在不同时间取样计算各成分的累积溶出百分率,采用相似因子f2进行溶出曲线相似性比较。结果对乙酰氨基酚、阿司匹林、咖啡因的安全线性范围分别为13.69～273.84μg/ml、18.18～363.60μg/ml、4.20～84.08μg/ml,r分别为1.0000、0.9999、0.9999。阿司匹林、咖啡因与对乙酰氨基酚的相似因子分别为28、78。结论高效液相色谱法简便、准确、重复性好,能准确测定复方对乙酰氨基酚片中3种主要成分的含量。试验结果表明该片剂中3种组分不具有同步溶出的特点。

Objective To establish a method for determination of paracetamol, asprin and caffeine in compound paracetamol tablets and measure the dissolution level of the three elements by use of it. Methods By use of high performance liquid chromatography （HPLC） , the Agilent C18 column was used, the mobile phase was methanol -0.05mol/L KH2PO4 （pH value was adjusted to 3.0 by using Sulfuric acid ） -Triethylamine （ 25 ： 75 ： 0.02 ）, the flow rate was 1.0ml/min, the detection wavelength was set at 272nm and column temperature was 30℃. Rotating basket method will be adopted to measure dissolution level with 1000ml hydrochloric acid solution as disslution media. The rotating speed is 100r/min and the temperature is 37± 0. 5~C. Took samples at different time and calculated the accumulated disslution percentage of the three elements. Then the similarity of the dissolution curves will be compared by using similarity factor （f2）. Results The linear calibration curve for paracetamol,asprin and caffeine was 13.69 ～ 273.84μg/ml （ r = 1. 0000）, 18.18 ～ 313.60μg/ml （ r = 0. 9999） ,4.20 ～ 84. 08μg/ml（r = 0. 9999） respectively. The similarity factor for the three elements was 28 and 78. Conclusion The HPLC method is simple, precise, good reproducibility and can be used to measure the content of main ingredient in compound paracetamol tablets. The dissolution level test indicates that the three elements dissolve at different time.