Li Lin-Li, Zhan Xian-Cheng, Tao Jian-Lin
Key Laboratory of Drug Targeting, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu 610041, China.
Arch Pharm Res. 2008 Mar;31(3):381-9. doi: 10.1007/s12272-001-1168-7. Epub 2008 Apr 13.
The influence of both moisture and heat on the stability of aspirin was investigated by a single pair of experiments, one with programmed humidity control and the other non-isothermal, rather than many standard isothermal studies, each at constant relative humidity. In experiments, we adopted the acid-base back titration method to measure the content of aspirin in the presence of its degradation products. It was found that the degradation of aspirin could be expressed as ln[(c0-c)/c]=kt+D, where D was a lag time item not related to humidity and temperature. The relationship between the degradation rate constant k and humidity Hr) and temperature T could be described as Arrhenius equation multiplied by an exponential item of relative humidity: k = A . exp(mHr) . exp(-(Ea/RT)), where A, Ea and m were the pre-exponential factor, observed activation energy, and a parameter related to humidity, respectively. The results obtained from the programmed humidifying and non-isothermal experiments, A=(1.09+/-2.04)x10(12) h(-1), Ea=(93.5+/-2.2) kJ . mol(-1) and m=1.18+/-0.19, were comparable to those from isothermal studies at constant humidity, A=(1.71+/-0.35)x10(12) h(-1), Ea=(94.9+/-0.7) kJ . mol(-1) and m=1.20+/-0.02. Since the programmed humidifying and non-isothermal experiments save time, labor and materials, it is suggested that the new experimental method can be used to investigate the stability of drugs unstable to both moisture and heat, instead of many classical isothermal experiments at constant humidity.
通过一对实验研究了湿度和温度对阿司匹林稳定性的影响，一个实验采用程序控湿，另一个采用非等温实验，而不是许多标准的等温研究（每个研究在恒定相对湿度下进行）。在实验中，我们采用酸碱返滴定法在阿司匹林存在降解产物的情况下测量其含量。结果发现，阿司匹林的降解可以表示为ln[(c0 - c)/c] = kt + D，其中D是与湿度和温度无关的滞后时间项。降解速率常数k与湿度Hr和温度T之间的关系可以描述为Arrhenius方程乘以相对湿度的指数项：k = A . exp(mHr) . exp(-(Ea/RT))，其中A、Ea和m分别是指前因子、观测活化能和与湿度相关的参数。程序控湿和非等温实验得到的结果A = (1.09 ± 2.04)×10(12) h(-1)、Ea = (93.5 ± 2.2) kJ . mol(-1) 和m = 1.18 ± 0.19，与恒定湿度下的等温研究结果A = (1.71 ± 0.35)×10(12) h(-1)、Ea = (94.9 ± 0.7) kJ . mol(-1) 和m = 1.20 ± 0.02相当。由于程序控湿和非等温实验节省时间、人力和物力，建议采用这种新的实验方法来研究对湿度和温度都不稳定的药物的稳定性，而不是许多经典的恒定湿度等温实验。
