对乙酰氨基酚片体外溶出与体内吸收的相关性评价

Evaluation on the in vitro Dissolution and in vivo Absorption Correlation of Acetaminophen Tablets

研究对乙酰氨基酚片在4种不同溶出介质的溶出行为和在兔体内的药动学过程,完成体内外相关性评价。首先以水、p H 1. 0盐酸溶液、p H 4. 5醋酸盐缓冲溶液、p H 6. 8磷酸盐缓冲溶液作为溶出介质,用转篮法进行体外溶出试验,然后以兔为体内试验对象,经口服给药后,由耳缘静脉取血;再通过紫外分光光度(UV)法测定对乙酰氨基酚片在这4种溶出介质中的溶出度以及在兔体内的血药浓度;由溶出数据可知该药在4种溶出介质中的溶出行为具有相似性,绘制血药浓度-时间曲线可知,6只兔子存在较大的个体差异;经DAS软件处理血药浓度可知该片在兔体内的药动过程符合一室模型,因此用Wagner-Nelson公式计算相应的体内吸收分数,然后评价体内外相关性。在这4种溶出介质中,体外累积溶出百分数与相对应时间点的体内吸收百分数之间的相关系数分别为0. 9448,0. 9198,0. 9540,0. 9378。结论:该片具有显著的体内外相关性。

The dissolution behavior of acetaminophen tablets in four different dissolution medium and the pharmacokinetics process of acetaminophen tablets in rabbits were studied in order to complete the evaluation of the in vitro and in vivo correlations of acetaminophen tablets. Water,p H 1. 0 hydrochloric acid solution,p H 4. 5 acetate buffer solution and p H 6. 8 phosphate buffer solution were used as four different dissolution medium in vitro. Then the blasket-rotating method was used to get on the dissolution testing in vitro. And the rabbits were used as the testing subjects in vivo. Then the rabbits got the tablets by oral administration and the blood of rabbits was taken from the ear vein. The Ultraviolet Spectrophotometry( UV) method was used to measure the cumulative dissolution of acetaminophen tablets in four different dissolution medium and the plasma concentration in rabbits. It could be seen from the dissolution data that the dissolution behaviour of acetaminophen tablets in this four dissolution medium was similar. Then draw the blood concentration-time curve. It could be seen from the blood concentration-time curve that there were large individual differences in six rabbits. The blood concentration data were dealt with DAS software. And the results showed that the pharmacokinetics process of acetaminophen tablets in rabbits was in compliance with the one-compartment model. For this reason the cumulative absorption percentage in vivo at the corresponding time was calculated by the Wagner-Nelson equation. Then the in vitro and in vivo correlation studies were performed by linear regression of the cumulative absorption percentage in vivo with the cumulative dissolution percentage in vitro. In this four different dissolution medium,the in vitro and in vivo correlation parameter were 0. 9448,0. 9198,0. 9540 and0. 9378,respectively. The acetaminophen tablets had the good correlation of in vitro dissolution and in vivo absorption.