克拉霉素缓释胶囊释放度与体内吸收度相关性的研究

摘要目的：研究两种释药机理的克拉霉素缓释胶囊试验制剂体内一体外相关性，建立与体内吸收相关的释放度测定法。方法：在不同pH介质中测定克拉霉素缓释胶囊的体外释放度。采用LC-MS-MS测定健康志愿者单剂量交叉口服250mg克拉霉素胶囊(F-1和F-2)后血药浓度，以Wagner—Nelson法计算药物的体内吸收百分数。以体外释放百分率对体内吸收百分数在相应的时间点进行相关性分析。结果：表明缓释胶囊F-1在pH5．0介质中释放百分率与体内吸收百分数相关，相关系数为0．9984，缓释胶囊F-2在pH6．0介质中释放百分率与体内吸收百分数相关，相关系数为0．9939。结论：经相关性检验，两种克拉霉素缓释胶囊的体外释放与体内吸收为水平A相关。F-1在体内的吸收程度高于F-2，为F-1的处方筛选提供了理论依据。

Studies on Correlation between in vitro Release and in vivo Absorption of Clarithromycin Modified Release Capsules

Objective; To investigate the in vitro - in vivo correlation of two clarithromycin modified release capsules and establish dissolution. Methods; The in vitro release characterstics of modified release capsules were evaluated at different pH conditions. The in vivo oral absorption were tested in healthy male volunteers and fractions absorbed were calculated by the Wagner - Nelson method. The concentrations of clarithromycin in plasma were determined by LC -MS -MS. Results:A linear correlation model was developed by using percent dissolved data and percent absorbed data from formulation - 1 (F - 1)and formulation -2(F -2) at the corresponding times. Dissolution conditions at pH 5. 0 predicted best the similarities in absorption rate and extents for F -1 ,and level A correlation coefficients was r = 0. 9984. Dissolution conditions at pH 6. 0 predicted best the similarities in absorption rate and extents for F -2,and level A correlation coefficients was r -0. 9939. Conclusions;The results of correlation test showed that F - 1 and F - 2 were level A in vitro - in vivo correlation, the results of this study were very useful in the development of F - 1.