兰索拉唑肠溶微丸胶囊的体外释放度与其在犬体内吸收的相关性评价

Study on the Correlation between in Vitro Dissolution and in Vivo Absorption in Dogs of Lansoprazole Enteric-coated Pellet Capsules

目的:考察兰索拉唑肠溶微丸胶囊的体外释放度与其在犬体内吸收的相关性。方法:采用紫外分光光度法,在245 nm波长处检测兰索拉唑肠溶微丸胶囊在酸(pH1.2)中1 h的累积释放度,在284 nm波长处检测其在磷酸盐缓冲液(pH6.8)中1.25 h的累积释放度;采用高效液相色谱法检测犬(n=6)灌服兰索拉唑肠溶微丸胶囊12 h内的血药浓度,以Wagner-Nelson法计算其体内吸收分数(fa),考察fa与体外释放度(f)t的相关性。结果:兰索拉唑肠溶微丸胶囊在酸中1 h的累积释放度<3%,在磷酸盐缓冲液中1.25 h的累积释放度>90%;该胶囊在犬体内2.5 h fa达最高值;在0.75～2 h内,fa=1.017 6ft-16.654(r=0.954)。结论:兰索拉唑肠溶微丸胶囊体外释放度与在犬体内吸收的相关性良好。

OBJECTIVE： To investigate the correlation between in vitro dissolution and in vivo absorption in dogs of lansoprazole enteric-coated pellet capsules.METHODS： UV spectrophotometry was adopted.Accumulative drug release rate of lansoprazole enteric-coated pellet capsules in acid solution（pH 1.2） was determined in 1 h at detection wavelength of 245 nm;that of drug in phosphate buffer solution（pH 6.8） was determined in 1.25 h at detection wavelength of 284 nm.The plasma concentration in beagle dogs after given lansoprazole enteric-coated pellet capsules in 12 h was measured by HPLC（n=6）.The in vivo absorption fraction（fa） was calculated by Wagner-Nelson method and the correlation of fa,and in vitro dissolution（ft） was investigated.RESULTS： Accumulative release rate of lansoprazole enteric-coated pellet capsules in acid solution was lower than 3% in 1 h,and that of drug in phosphate buffer solution was higher than 90% in 1.25 h;the absorption fraction fa reached the peak in 2.5 h;fa=1.017 6ft-16.654 within 0.75～2 h（r=0.954）.CONCLUSION： The dissolution in vitro of lansoprazole enteric-coated pellet capsules is well correlated with absorption rate in vivo.