【摘要】 本文用隔室模型分别来描述药物在体外和体内的过程，并建立了药物在体内、外的动力学方程。通过求算方程中的体内、外港出速度参数Ｒ(ｉｎ)和Ｒ(ｏｕｔ)来评价药物的体内外相关性。采用模型药物盐酸曲马多的体内外数据，根据建立的动力学方程，用自编程序计算在０、２５、１００ｒｐｍ条件下的体外溶出参数Ｒ(ｏｕｔ)的值分别为９.０３±２．０３ｘ１０(－５)ｍＬ．ｍｇ(－２／３)ｍｉｎ(－１)，１.６３±０.９０ｘ１０(－４)ｍＬ·ｍｇ(－２／３)ｍｉｎ(－１)，１８０±０.６５ｘ１０(－４)ｍＬ·ｍｇ(－２／３)·ｍｉｎ(-1)，体内溶出参数Ｒ(ｉｎ)的值为６．２７±０.５２ｘ１０(－５)ｍＬ·ｍｇ(－２／３)·ｍｉｎ(－１)。结果表明，在上述三个不同转数的情况下，体外溶出参数Ｒ(ｏｕｔ)比体内溶出参数Ｒ(ｉｎ)稍大。据此，可以通过调整体外溶出条件进而能更精确地模拟体内溶出情况。更多还原

【Abstract】 A dissolution model and a dissolution-absorption model were used to describe invitro and in vivo fates of drug dosage forms. Accordingly, two groups of equations were developed todisplay the kinetic processes of the two models. Considering that an in vitro dissolution test was usednot to simulate the absorption of drugs in vivo but to approach its in vivo dissolution behavior, the invitro dissolution rate constant Rout, and the in vivo dissolution rate constant Rin were selected to evaluate the correlation between the in vitro and in vivo processes. Two computer programs were developed to simulate the in vitro and in vivo processes respectively, thereby providing the approximationof Rout and Rin In this simulation, an absorption rate constant Ka (obtained from conventional pharmacokinetic simulation) of drug solution was used to substitute the absolute absorption rate constant Kab(which means the absorption rate constant of a completely dissolved drug solution at the absorptionsite) of the drug to obtain Rin. Two dosage forms of tramadol hydrochloride (capsule and oral solution)were orally administered to six healthy volunteers and blood samples were assayed with a HPLC procedure with fluorescence detection. The data of oral solution were used to obtain the approximation ofKab.In vitro dissolution test was also performed with the capsule. After the computer-aided simulationon the data obtained from the capsule, the mean Rin for six volunteers was 6.27±0.52×10-5 mL.mg-2／3min-1 and the mean Rout, of six samples at 0, 25, 100 rpm stirring rate in dissolution test was9.03±2.03×10-5, 1.63±0.90×10-4 and 1 .80±0.65×10-4 mL.mg--2/3.min-1, respectively. These results mightsuggest that compared with Rin, Rout, values were higher to some extent, which means that the dissolution test method used here achieved a faster dissolution rate than that of the in vivo. The dissolutiontest at 0 rpm stirring rate provided a relatively approximate result, even though it still seemed to be alittle faster This work might introduce a method to evaluate the in vitro and in vivo correlation and todirect the improvement of an in vitro dissolution test.更多还原