初均速加速试验法研究温度和湿度对药物稳定性的影响

Evaluation of the influence of humidity and temperature on the drug stability by initial average rate experiment

目的:采用初均速加速试验法研究温度和湿度对药物稳定性的协同影响规律,并获得相关降解动力学参数。方法:首先通过计算机模拟探讨加速试验方法、含量误差、药物降解程度、温度和湿度组数、温湿度差、平均温湿度等因素对初均速加速试验测定结果的影响规律;然后以维生素C为模型药物,采用初均速加速试验法获得药物的降解动力学参数。结果:试验结果表明在试验条件相同的情况下,初均速加速试验测定结果的准确度和精密度与经典恒温恒湿加速试验基本一致,且实验工作量明显减小。结论:初均速加速试验可以应用于考察温度和湿度对药物稳定性的协同作用,预测药物有效期。

Objective: To evaluate the inl uence of temperature and humidity on the drug stability by initial average rate experiment, and to obtained the kinetic parameters. Methods: The effect of concentration error, drug degradation extent, humidity and temperature numbers, humidity and temperature range, and average humidity and temperature on the accuracy and precision of kinetic parameters in the initial average rate experiment was explored. The stability of vitamin C, as a solid state model, was investigated by an initial average rate experiment. Results: Under the same experimental conditions, the kinetic parameters obtained from this proposed method were comparable to those from classical isothermal experiment at constant humidity. The estimates were more accurate and precise by controlling the extent of drug degradation, changing humidity and temperature range, or by set ing the average temperature closer to room temperature.Conclusion: Compared with isothermal experiments at constant humidity, our proposed method saves time, labor, and materials.