平面单测点法评价湿度和温度对药物稳定性的影响

Evaluation of the Influence of Humidity and Temperature on the Drug Stability by Plane Single Time Point Experiments

利用均匀设计分散原理,确定药物的湿度温度平面,采用单测点法获得药物相关的降解动力学参数.阿司匹林稳定性加速试验结果表明,平面单测点法与恒温恒湿法和程序变温变湿法得到的降解动力学参数基本一致.在药物降解程度及试验的湿度差和温度差相同的条件下,平面单测点法结果的准确度和精密度均明显优于程序变温变湿法,且装置简单.与经典恒温恒湿法相比,平面单测点法的误差较大,但试验工作量减少.

The moisture and temperature plane of a drug was determined based on the dispersive principle of uniform design. Then, kinetic parameters were obtained by a single time point experiment. The stability of aspirin, as a solid state model, was investigated. We found that the results obtained from this proposed method were comparable to those from isothermal studies at constant humidity and also comparable to those from the programmed humidifying and heating experiments. Under the same experimental conditions, the estimates of the kinetic parameters （Ea, m, A） obtained from the new method were significantly more accurate and precise than those obtained from the programmed humidifying and heating experiments. No specific computer-controlled environmental chamber needs to be used in our new method. By comparison to isothermal experiments at constant humidity, our proposed method saved time, labor, and materials.