A Simplified Approach For Predicting Drug Degradation In Parenteral Solution Products During Moist Heat Sterilization Process

Objective:It's known that there will be certain amount of degradants generated after experiencing sterilization under high temperature for heat-sensitive drug injections.To save the developmental time and economical cost,this study is to establish an approach of simplifying the mathematical modeling to predict the concentration of degradants after sterilization.Method:This study applied the illustrative example of Ornidazole injection through designing a lot of experiments including multiple formulations(various pH values)and multiple sterilization processes(various F0 values),and obtained sufficient data including pH,concentrations of Ornidazole,concentrations of related substance of D at pre-sterilization and post-sterilization respectively.Meanwhile,the instant temperature and F0 at different locations of the vessel during multiple sterilization processes were collected to plot Temperature-Time curve and FO-Time curve.This study is scientifically based upon the mathematical rate equation of increased degradants,integral equation of degradants'concentration and the equation of rate constant of a chemical reaction,and is to simplify the calculation process of establishing the predicting model for specific chemical reactions in support of the analysis of the common characteristics of a moist-heat sterilization process and the analysis of drug/pH change profile during sterilization process.Conclusion:Established a simplified model to predict impurity levels after moist-heat sterilization.The approach of building the model can be well applied in Injections.