Step Nonisothermal Method to Study Stability of Drugs

Abstract

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 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 k₀) 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.

Keywords:

• captopril
• drug stability
• step nonisothermal experiment
• oxidative degradation kinetics
• optimization
• computer simulation

ACKNOWLEDGMENT

We are thankful for the financial support of the National Natural and Science Foundation of China (No. 30472104).