应用体内外相关性模型研究红霉素缓释微囊的体内外相关性

Study on in vitro-in vivo correlation of erythromycin mkrocapsules using in vitro -in vivo correlation models

目的 对红霉素缓释微囊的体内外相关性进行了研究,并对模型在预测体内数据方面的性能进行了考察。方法 应用美国缓、控释制剂专业委员会推荐的水平A、水平B两种体内外相关的模型。收集红霉素缓释微囊12 h的体外溶出数据。同时以家兔为实验动物,灌服微囊后收集血药浓度。应用水平A相关性模型,采用反卷积方法获得体内吸收百分数,并与体外溶出百分数进行比较。同时进一步运用基本的和扩展的卷积-反卷积方法对微囊的体内外相关性进行研究。对水平B相关性模型在药物相关性研究上的应用也进行了考察。结果 水平A模型和水平B模型都得到比较好的结果。结论 两种模型都能刻画体内外的相关性,水平A相关性模型可以得到较水平B相关性模型更多的关于药物体内外相关性的信息。

OBJECTIVE: To evaluate the internal predictive ability of level A and B in vitro-in vivo correlation (IVIVC) models for erythromycin microcapsules. METHODS: In vitro dissolution data of erythromycin microcapsules were collected for 12 h. Plasma concentration data were obtained from 6 rabbits after administration erythromycin microcapsules, in two absorption percentage was obtained by a deconvolution-based level A model and compared with the in vitro dissolution. Further, basic and extended convolution level A IVIVC models were applied to investigate the in vitro-in vivo correlation of erythromycin microcapsules. Internal predictiveability of level A and level B was assessed by comparing observed and predicted plasma concentration data and by comparing in vitro dissolution time (MDT) and in the dissolution time (MRT). RESULTS: Both A and B models can describe the in vitro-in vivo correlation. CONCLUSION: Level A and B models have good internal predictiveability, and level A is better than level B.