盐酸多西环素注射液的稳定性研究

Studies on stability of doxycycline hydrochloride injection

为确定盐酸多西环素注射液的有效期和包装运输条件,以高效液相色谱法测定多西环素的含量变化,评价制剂对温度和光照的稳定性。温度加速试验采用经典恒温法,考察温度为65、75、85和95℃,每一温度设5个不同的采样时间点,根据动力学和Arrhenius指数定律计算稳定性的相关参数。光照试验分裸露组和包装组,在照度(4 500±500)lx条件下放置10 d,于第5 d和第10 d检测样品。温度加速试验表明多西环素的分解反应为一级动力学反应,k25℃为5.319 7×10-6/h,25℃时t0.9为2.26年。光照试验表明盐酸多西环素注射液对光照敏感,裸露组的药物含量、pH值和颜色均有明显变化;稳定性试验结果表明盐酸多西环素注射液在25℃、避光条件下的有效期可暂定为24个月。

To establish expiration time and suitable package and transport conditions for doxycycline hydrochloride injection,the changes of doxycycline with temperature and illumination were determined by high performance liquid chromatography（HPLC） with UV detector. Temperature-accelerated tests by the classic homeothermia method were performed at 65℃ ,75℃ ,85℃ and 95℃ ,respectively,with 5 different time points in each temperature. Stability parameters were computed by reaction kinetic equation and Arrhenius exponential law. Illumination tests including exposure group and package group were carried out by place for 10 days at illumination level of（4 500±500） lx and the samples were determined on day 5 and 10. Results of temperature-accelerated tests indicated that the rate process of doxycycline degradation in doxy- cycline hydrochloride injection was a first-order kinetics with k25c of 5. 319 7 X 10^-6/h and to,9 of 2. 26 years. Results of the illumination tests indicated that the doxycycline hydrochloride injection was instable for light because contents of doxycycline,pH values and color in the exposure group changed markedly in the package group. The stability tests demonstrated that the expiration time of the doxycycline hydrochlo- ride injection was 24 months at 25℃ ,away from light.