关键词: 体内外相关性, 溶出, 模拟, 盐酸曲马多

Abstract: A dissolution model and a dissolution-absorption model were used to describe in vitro 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 in vitro 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^-2/3 min^-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.

Key words: Correlation, Dissolution, Simulate, Tramadol hydrochloride