老化对格列吡嗪控释片中丙酮残留、体外释放和生物等效性的影响

Effects of aging on acetone residue,in vitro release and bioequivalence in Glipizide controlled release tablets

目的考察了不同老化工艺对格列吡嗪控释片丙酮残留、释放曲线及人体内生物等效性的影响。方法采用气相色谱法测定丙酮残留,考察不同老化工艺对丙酮的去除效率的影响;采用高效液相色谱法检测溶出曲线,考察自研制剂的体外释放情况并与参比制剂进行释放曲线相似因子f_(2)比较。采用随机、开放、单剂量、两周期双交叉实验设计,对比自制样品与参比制剂的在人体内的生物等效性情况。结果当老化温度为50℃、相对湿度为65%时,丙酮去除的效率最高,能在24小时或更短时间内使得丙酮残留量符合标准要求,又能达到与参比制剂在体外释放行为一致,体内关键药代动力学参数一致。结论该老化方法操作简单,能满足自制样品与参比制剂质量与疗效的一致。

Objective The effects of different aging processes on acetone residue,release curves and bioequivalence in human of Glipizide controlled release tablets were investigated.Methods The effects of different aging processes on the removal efficiency of acetone were investigated by gas chromatography.The dissolution curves were detected by High-performance liquid chromatography(HPLC).The release of the test tablet was investigated and the similarity factor f_(2) of the release curves were compared with that of the reference tablets.A randomized,open,single-dose,two-cycle double-cross experiment design was used to compare the bioequivalence between the test tablets and the reference tablets in human.Results The results indicated that the removal efficiency of acetone was the highest at the temperature of 50℃ and the humidity of 65%,which could make the residual of acetone meet the standard in 24 hours or less,and can achieve consistent release behavior in vitro and consistent key pharmacokinetic parameters in vivo with the reference tablets.Conclusions The aging method is simple to operate and can satisfy the quality and efficacy of test preparation and reference preparation.