摘要
目的采用加速稳定性评估程序(ASAP)建立奥贝胆酸片的降解动力学模型,在较短时间内评估其长期稳定性。方法基于奥贝胆酸片的杂质Ⅰ限度,通过ASAPprime软件设计实验方案,将药品裸片暴露于50℃~70℃温度和0%~81%RH相对湿度条件下至多21 d,使用高效液相色谱检测杂质Ⅰ的含量。将结果输入软件中,采用湿度校正的Arrhenius方程和等转换方法分析数据创建预测模型,评估奥贝胆酸片的长期稳定性。结果降解动力学模型拟合良好,拟合参数R^(2)>0.9,Q^(2)>0.9。长期条件下杂质Ⅰ增长预测值与实测值接近,证实了模型的可靠性。结论本文建立的降解动力学模型能够在较短时间内准确预测奥贝胆酸片杂质Ⅰ的增长情况,能够为后续稳定性方案的制定提供数据支持。
OBJECTIVE To establish the degradation kinetic model of obeticholic acid tablets in combination with the accelerated stability assessment program(ASAP),and evaluate its long-term stability in a short period of time.METHODS Based on the impurity I limit of the drug,the accelerated stability experiment plan was designed through the ASAPprime software,oberylcholic acid tablets were exposed at the temperature from 50 to 70℃,and the relative humidity conditions from 0%to 81%RH for up to 21 days.High-performance liquid chromatography was used to analyze the content of impurity I.These data were then analyzed using ASAPprime with humidity correction to create a shelf-life predicting model,so as to predict the long-term stability of obeticholic acid tablets.RESULTS The degradation kinetics model fitted well.The fitting parameters R^(2)>0.9,Q^(2)>0.9.The predicted value of impurity I growth under long-term conditions was closed to the measured value,which confirmed the reliability of the model.CONCLUSION The degradation kinetics model established in this paper can effectively predict the growth of impurity I of obeticholic acid tablets,which can be used as data support for the formulation of the follow-up stability plan.
作者
张亚茹
章晓骅
徐丹
ZHANG Yaru;ZHANG Xiaohua;XU Dan(Institute of Research,Nanjing CHIA TAI TIANQING Pharmaceutical Co.,Lud.,Nanjing,Jiangsu210046,China)
出处
《今日药学》
CAS
2022年第7期520-523,539,共5页
Pharmacy Today
关键词
降解动力学模型
奥贝胆酸片
ASAP
稳定性评估
degradation kinetic model
obeticholic acid tablets
ASAP
stability prediction
