Rapid Headspace Oxygen Analysis for Pharmaceutical Packaging Applications

Molecular oxygen is involved in the propagation step of this reaction, and it is an integral part of the catalytic cycle that generates the oxidative degradation of drug substances in pharmaceutical formulations. Oxidative degradation of the active drug substance in a formulation decreases drug potency and reduces product shelf life (2). The rate of oxidative degradate formation is proportional to the structural susceptibility of the specific drug substance to auto-oxidize and to storage (reaction) conditions such as temperature, humidity, oxygen concentration, and time. Other deleterious effects of oxidative processes include product discoloration, changes in dissolution rate and profile, precipitation, and the generation of foul odors and flavors (1). Most important, oxidative degradation products generated in the final pharmaceutical product during storage may also have adverse pharmacological properties, including those associated with toxicity or negative side effects. Drug oxidation can also pose significant challenges during manufacturing processes, particularly for easily oxidized drug substances. The effects are especially pronounced in formulations that require manufacturing unit operations to be performed in solutions or suspensions. In such cases, extra care may be required to minimize or eliminate exposure to oxygen. Inert-gas purging to lower solution oxygen levels as well as inert blanketing of process vessels have long been used in parenteral manufacturing processes. Besides purging at key manufacturing steps — for example, during drug compounding or while holding a drug in solution before lyophilization — packaging with an inert blanket over the final product also protects parenteral formulations that are susceptible to oxidation. Removing Initiation