PURPOSE: Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation. METHODS: Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40 degrees C. The oxidative degradation was quantified as a function of time. RESULTS: The results clearly show dependence of oxidative degradation on headspace oxygen concentration, relative humidity, drug loading and time. CONCLUSIONS: The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.
PURPOSE: Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation. METHODS: Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40 degrees C. The oxidative degradation was quantified as a function of time. RESULTS: The results clearly show dependence of oxidative degradation on headspace oxygen concentration, relative humidity, drug loading and time. CONCLUSIONS: The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.
Authors: Kenneth C Waterman; Roger C Adami; Karen M Alsante; Jinyang Hong; Margaret S Landis; Franco Lombardo; Christopher J Roberts Journal: Pharm Dev Technol Date: 2002-01 Impact factor: 3.133