Step nonisothermal method to study stability of drugs.
A step nonisothermal experiment under high oxygen pressure and a new computation with optimization for step nonisothermal experiment on stability study of drugs was introduced. The kinetics parameters of captopril oxidation in aqueous solution were determined by this method. It is reported that the reaction of captopril solution occurs under either aerobic or anaerobic condition, giving different products. Then the total rate constant k(total) can be expressed as [image omitted] where k(anaerobic) and k(aerobic) are the rate constants of anaerobic and aerobic degradations, respectively. The results indicated that the parameters obtained in the step nonisothermal experiment were comparable with those obtained in the isothermal-isobaric experiments. By a computer simulation, the estimates for the kinetic parameters (E(a) and k(0)) obtained with step nonisothermal method were statistically evaluated. Results indicated that the estimates obtained with isothermal-isobaric method were somewhat more precise than those obtained with step nonisothermal method. However, the experimental period needed by isothermal-isobaric method was much longer than that needed by step nonisothermal method.
Lin
Bing
B
Key Laboratory of Drug Targeting, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, P.R. China.
Zhan
Xian-Cheng
XC
Tao
Jian-Lin
JL
Li
Lin-Li
LL
Qi
Hai-Jun
HJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry*; D004355:Drug Stability; D007700:Kinetics; D008432:Mathematical Computing; D010084:Oxidation-Reduction; D010100:Oxygen; D010313:Partial Pressure; D012996:Solutions; D013696:Temperature; D014867:Water
D000806:Angiotensin-Converting Enzyme Inhibitors; D012996:Solutions; D014867:Water; D002216:Captopril; D010100:Oxygen