Regulatory Notes on Impact of Excipients on Drug Products and the Maillard Reaction

In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.