Zhan X, Yin G, Wang L, Ma B
School of Pharmacy, West China University of Medical Sciences, Chengdu, Sichuan, People's Republic of China.
J Pharm Sci. 1997 Jun;86(6):709-15. doi: 10.1021/js960398q.
A new nonisothermal heating model (exponential heating model) for drug stability experiments, based on a theoretical study of simulated nonisothermal data, is presented. In the model, the heating rate dT/dt is increased by 2-4 times at every increase of 10 degrees C in temperature: dT/dt = a(T-T0)/10.(dT/dt)0 where a is the times by which the heating rate is increased at every increase of 10 degrees C. A computation method with optimization and Simpson integration for the experiment was also introduced. The estimates for the shelf-life and activation energy obtained by the exponential and other nonisothermal heating models were statistically evaluated and were compared with those obtained by the isothermal method under various conditions. The results indicated that under the same experimental conditions, the estimates obtained by the exponential heating model were significantly more accurate and precise than those obtained by the linear, reciprocal, and logarithmic heating models. The accuracy and precision of the estimates were independent of the shelf-life of drugs and experimental period. The estimates obtained by the isothermal method were somewhat more accurate and precise than those obtained by the exponential heating model. However, the experimental period needed by the isothermal method was about five times longer than that needed by the exponential heating model. The results also showed that in each of the heating models, the estimates are more accurate and precise by increasing the extent of drug degradation, changing temperature range or sampling frequency, or by having the mean temperature closer to room temperature. To demonstrate its applicability, the exponential heating model was used to study the stability of vitamin C tablets and predict their shelf-life.
基于对模拟非等温数据的理论研究，提出了一种用于药物稳定性实验的新型非等温加热模型（指数加热模型）。在该模型中，温度每升高10℃，升温速率dT/dt增加2至4倍：dT/dt = a(T - T0)/10·(dT/dt)0，其中a是温度每升高10℃时升温速率增加的倍数。还介绍了一种用于该实验的具有优化和辛普森积分的计算方法。对通过指数和其他非等温加热模型获得的保质期和活化能估计值进行了统计评估，并与在各种条件下通过等温方法获得的估计值进行了比较。结果表明，在相同的实验条件下，指数加热模型获得的估计值比线性、倒数和对数加热模型获得的估计值显著更准确和精确。估计值的准确性和精确性与药物的保质期和实验周期无关。等温方法获得的估计值比指数加热模型获得的估计值略更准确和精确。然而，等温方法所需的实验周期比指数加热模型所需的实验周期长约五倍。结果还表明，在每个加热模型中，通过增加药物降解程度、改变温度范围或采样频率，或使平均温度更接近室温，估计值会更准确和精确。为证明其适用性，指数加热模型被用于研究维生素C片的稳定性并预测其保质期。
