Therapeutic drugs require a well characterized shelf-life to ensure correct dosage and patient safety. Degradation processes quite often involve free radicals and transition metals that are responsible for the majority of the damage that occurs in drug products. By analyzing an EPR signal, one can identify, quantify and monitor temporal behavior of the free radicals involved in product degradation.
Forced oxidation, also known as “stress testing,” is routinely used in pharmaceutical development to predict the stability of drug products that affects purity, effectiveness, and safety. In stress testing, the drug product is often exposed to heat, light or chemical agents with the goals being to understand degradation pathways, determine intrinsic stability and shelf-life, develop stable formulations, and evaluate antioxidant efficiency.
Pharmaceutical regulations require more fundamental understanding of the chemistry involved in API production, including reactive intermediate identification. The surge of new molecules that exhibits specific properties is vital to pharmaceutical development, and EPR reaction monitoring is a critical step in optimizing the synthesis of new drugs.
Additionally, understanding reaction mechanism can lead to cost savings and high-quality final products. Chemistry involving radicals and transition metals is an integral component of maximizing product yield and minimizing environmental footprint.
Proper sterilization of surfaces is important in pharmaceutical manufacturing, equipment and packaging, as well as the pharmaceuticals themselves. The most commonly used sterilization processes are gamma or electron beam irradiation, dry heat, and pressure. These processes generate free radicals that are responsible for degradation of the irradiated materials, and cause alteration of the physicochemical properties of the sterilized product. This can also decrease drug potency by partial decomposition during sterilization and may be a toxicological hazard.
All drugs contain impurities that can arise from APIs, excipients, or both. They can also be introduced into the drug during formulation, packaging, and storage. Impurities have many unwanted effects, including decreasing the therapeutic effect, lowering the product shelf life and inducing toxicity. Organic impurities are often free radicals from byproducts, intermediates, or degradation processes, while inorganic impurities are frequently transition metals. EPR spectroscopy with its high sensitivity can detect traces of impurities down to parts-per-billion levels.