A Rapid Technique to Evaluate the Oxidative Stability of a Model Drug

ABSTRACT

The objective of the current study was to investigate the oxidative induction time (OIT) as a measurement of the stability of an oxygen-sensitive model drug. The OIT was determined by differential scanning calorimetry and represents the time required for oxidative decomposition to occur at a given temperature. Samples were heated to a specific temperature under a nitrogen blanket then held isothermal while exposed to oxygen. The experiment proceeded until oxidative degradation of the sample was apparent from the real-time heat flow graphs. Variables investigated in this study included different lots and suppliers of a model drug as well as the addition of antioxidants. Results demonstrated that the stability of the drug was dependent on the supplier. All antioxidants investigated in this study improved oxygen stability of the model compound, as evidenced by a longer OIT. Butylated hydroxyanisole (BHA) was found to better stabilize the drug than butylated hydroxytoluene at equivalent concentrations. The combination of ascorbic acid and BHA provided the greatest protection against oxidation of the model compound. The results of this study demonstrate the usefulness of OIT to investigate the oxygen stability of pharmaceutical compounds.

KEYWORDS:

• Oxidation
• Degradation
• Stability
• Antioxidants
• Differential scanning calorimetry (DSC)
• Oxidative induction time (OIT)