Hekimoğlu S, Ayanoğlu-Dülger G, Hincal A A
Int J Clin Pharmacol Ther Toxicol. 1987 Feb;25(2):93-6.
Three brands of acetaminophen tablets marketed in Turkey were evaluated for their in vitro properties, and their in vivo bioavailabilities were determined in comparison to a standard acetaminophen solution containing an equivalent amount of the drug. The total amount of acetaminophen in urine or in tablets was determined by the colorimetric method of Welch and Conney [1965]. No significant difference between the manufacturing parameters, namely the assay, hardness, diameter and thickness of the brands was observed except that the coefficients of variation for brand A were greater than the other two brands. Brand A also disintegrated more slowly and its dissolution time (80% of the drug dissolved in 45 min) did not meet the requirements of USP XX. In vivo bioavailability studies were carried out in six healthy volunteers who received the tablets or the standard solution in a single dose, cross-over study. The urine was collected for 24 h and the total acetaminophen excreted was determined according to the method of Welch and Conney. The relative bioavailabilities for Brands A, B and C were found to be 97.87, 95.41 and 98.78%, respectively, with respect to the solution. The differences were not statistically significant and it can be concluded that all tablets were rapidly and almost completely absorbed. This study also demonstrates that there is not always a good correlation between the in vitro disintegration and dissolution tests and the in vivo bioavailability of a drug.
对在土耳其销售的三种品牌的对乙酰氨基酚片进行了体外性质评估,并与含有等量药物的标准对乙酰氨基酚溶液相比,测定了它们的体内生物利用度。采用Welch和Conney [1965]的比色法测定尿液或片剂中对乙酰氨基酚的总量。除了品牌A的变异系数大于其他两个品牌外,各品牌的生产参数,即含量测定、硬度、直径和厚度之间未观察到显著差异。品牌A的崩解也更慢,其溶解时间(45分钟内80%的药物溶解)不符合美国药典XX的要求。在六项健康志愿者中进行了体内生物利用度研究,他们接受了片剂或标准溶液的单剂量交叉研究。收集尿液24小时,并根据Welch和Conney的方法测定排泄的对乙酰氨基酚总量。相对于溶液,品牌A、B和C的相对生物利用度分别为97.87%、95.41%和98.78%。差异无统计学意义,可以得出结论,所有片剂均能快速且几乎完全吸收。该研究还表明,药物的体外崩解和溶解试验与体内生物利用度之间并不总是具有良好的相关性。