Evaluation of the stability of aspirin in solid state by the programmed humidifying and non-isothermal experiments.
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.
Li
Lin-Li
LL
Key Laboratory of Drug Targeting, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu 610041, China. ysylilinli@sina.com
Zhan
Xian-Cheng
XC
Tao
Jian-Lin
JL
D001241:Aspirin / Q000737:chemistry*; D004304:Dosage Forms; D004355:Drug Stability; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D017186:Titrimetry; D014867:Water / Q000737:chemistry*
D004304:Dosage Forms; D014867:Water; D001241:Aspirin