非诺贝特纳米混悬剂溶出度测定与体内吸收的相关性评价

Study on the Correlation between Dissolution in Vitro and Absorption in Vivo of Fenofibrate Nanosuspension

关键词:  非诺贝特  纳米混悬剂  溶出度  Wagner-Nelson法  体内外相关性

Key words:  fenofibrate  nanosuspension  issolution  Wagner-Nelson method  in vivo-in vitro correlation

摘要:

目的 考察非诺贝特纳米混悬剂、原料药粉、微粉化原料药粉的体外溶出特性，研究比较三者在大鼠体内的生物利用度，并对其体内外相关性作出评价。方法 以紫外分光法测定体外溶出度；以高效液相色谱法测定大鼠灌胃给药后的血药浓度；以Wagner-Nelson法计算体内吸收分数，考察体内吸收与体外溶出的相关性。结果 纳米组AUC0-36h 和Cmax分别为原料组、微粉组的10倍和2倍，纳米混悬剂组体内吸收分数fa与体外溶出速率ft的关系为：fa=4.407 9ft- 303.31，r=0.983 8。结论 与原料和微粉组相比，非诺贝特制成纳米混悬剂后，药物的溶出速度和生物利用度均有显著提高，体外溶出与体内吸收相关性良好。

Abstract:

OBJECTIVE The dissolution rate in vivo and bioavailability in rats of fenofibrate nanosuspension, coarse and microsize suspension were investigated. The correlations of the drugs in vitro-in vivo were also evaluated. METHODS The drug dissolutions in vitro were measured by UV spectrophotometer, and the plasma concentrations in rats were measured by HPLC. The correlations were studied by the test of dissolution in vitro and bioavailability in vivo through Wagnner-Nelson method. RESULTS The AUC0-36h and C_max of the nanosuspensions were about 10-fold of the coarse and 2-fold of the microsize suspension. The relationship between the dissolution fraction and the absorption fraction was: fa=4.407 9ft-303.31, r=0.983 8. CONCLUSION The dissolution and bioavailability of nanosuspensions enhanced greatly compared with the coarse and microsize suspension. There were good correlationships between dissolution rate in vitro and absorption rate in vivo.