摘要
目的评价两种规格5-单硝酸异山梨酯缓释胶囊(5-ISMN-SRC)体外释放度与体内吸收的相关性,为5ISMNSRC的质量控制提供依据。方法应用ZRS8G智能溶出仪和高效液相色谱法(HPLC)测定两种规格5-ISMN-SRC(25、50mg)在两种pH介质(pH为1.0和6.8)中的释放度;采用气相色谱法(GC)测定志愿受试者分别口服两种规格药物后不同时间的血药浓度(n=22、21),按WagnerNelson公式计算一定时间段药物的体内吸收百分率。结果两种规格5-ISMN-SRC在pH为1.0和6.8介质中的体外释药行为基本符合零级动力学过程,5ISMN释放与pH无明显关系。口服5-ISMN-SRC,规格为25mg较50mg的体内药动学参数AUC0T、AUC0∞和Cmax显著降低(P<0.01),但Tmax无明显差异(P>0.05)。两种不同介质(pH为1.0和6.8)的体外累积释放百分率与体内吸收百分率的回归分析表明,5-ISMN-SRC为25mg规格的相关系数r为0.9641和0.9526,50mg的相关系数r为0.9846和0.9680,均大于临界值r1-0.01。结论两种规格5ISMNSRC的体外释放度与体内吸收具有显著的相关性。
Objective To evaluate in vitro release and in vivo absorption of two strengths of isosorbide-5-mononitrate sustained-release capsules(5-ISMN-SRC). Methods In vitro release of 5-ISMN-SRC in two pH media (pH 1.0 and pH 6.8) was determined with ZRS-8G dissolution tester and by high-performance liquid chromatography(HPLC). The plasma levels after a single dose of 5-ISMN-SRC (25 mg, 50 mg)in healthy volunteers were determined by gas chromatography, and the absorption fractions were calculated according to Wagner-Nelson's formula. Results Similar release rates of two strengths of 5-ISMN-SRC were obtained in two different pH media with zero order kinetics. Medium pH variation did not affect in vitro release of 5-ISMN. After oral administration of 25 mg and 50 mg 5-ISMN-SRC, significant differences were found in AUC 0-T、AUC 0-∞ and C max, but not in T max. The correlation coefficients (r) between in vitro dissolution in pH 1.0 and pH 6.8 media and in vivo absorption fractions were 0.9641 and 0.9526 for 25 mg 5-ISMN-SRC, and 0.9846 and 0.9680 for 50 mg 5-ISMN-SRC. Conclusion There is significant correlation between in vitro release and in vivo absorption of two strengths of 5-ISMN-SRC.
出处
《上海第二医科大学学报》
CSCD
北大核心
2005年第6期575-578,共4页
Acta Universitatis Medicinalis Secondae Shanghai
