Excipients peroxide impurities

Peroxides are a very common impurity in many excipients, particularly polymeric excipients [56]. They are used as initiators in polymerisation reactions, but are difficult to remove. Ding [57] monitored the peroxide concentrations within polysorbate 80 solutions, and demonstrated the effect of light, heat and concentration on peroxide concentrations. The author showed that the peroxide concentrations increased 9-fold at the lowest polysorbate concentration versus increases of only 1.5-fold at the highest polysorbate concentration. However, the absolute peroxide levels at the higher concentration were much higher. 

The quality of each excipient should be taken as another potential source of instability in an oral solution. For example, a company may rely on the certificate of analysis of an excipient for proof of its purity. However, in solution, the reactivity of any impurity may become especially significant. For example, undetermined trace amounts of peroxides, from excipients such as polyvinyl pyrrolidone, are known... 

Hydrogen peroxide is a good test to produce selected degradation impurities, but also has some predictive value. Sensitivity to hydrogen peroxide can predict interaction with peroxide generating excipients. Moreover, a positive result of both AIBN and hydrogen peroxide is a strong evidence that the test substance is susceptible to oxidation. 

Numerous specifications and control measures are employed to determine final product quality, the first of which is ensuring adequate quality of excipients and active ingredients. Excipient testing ensures compliance with compendial specifications, as well as specifications determined during development of the fill material and/ or shell formulation. Among these are limiting values for trace impurities, especially peroxides, aldehydes, some metals, and ionic salts. 

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