Interactions between excipient impurities and other elements of a product can have a significant detrimental impact on finished drug stability. Consequently, manufacturers, even if they have a stable active pharmaceutical ingredient (API), can find themselves with an unstable finished drug.
A roundtable session at AAPS 2010, entitled “Reactive Impurities in Excipients: Characterization and Stabilization Strategies”, discussed how ingredients suppliers and pharma manufacturers can mitigate these issues.
Shaukat Ali, technical services manager at BASF, said “packaging is very important in controlling degradation” and, in light of this, the company is using in-liners. Tests at BASF have shown use of in-liners in excipient packaging has a significant impact on controlling peroxide levels.
Peroxide is generated during oxidative degradation of the excipient. Polymeric ethers, such as polyethylene glycol (PEG), are prone to this process and require particular attention.
Film coatings and aluminium lakes
Thomas Farrell, director of product development at Colorcon, discussed strategies to control the presence of formaldehyde and formic acid in film coatings. In particular, Farrell highlighted recent, as yet unpublished, Colorcon research into the impact of aluminium lakes on impurity formation.
Colorcon found using red 30 and red 40 aluminium lakes kept impurity levels much lower. It is currently unclear what process underpins this but it appears the present of aluminium lakes suppresses impurity formation.
PEG use
Ali said producing PEG with low levels of peroxide and aldehyde is a very complex process that requires significant levels of expertise. This limits the number of companies in the market.
For pharma formulating products with PEG Farrell gave a number of recommendations to minimise stability issues. These include decreasing levels of PEG-containing excipients, exploring the substitution of PEG and examining the temperature dependency of degradation.