US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
AAPS PharmSciTech. 2018 Feb;19(2):965-969. doi: 10.1208/s12249-017-0878-y. Epub 2017 Sep 25.
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.
一般来说，辅料在制剂药品的整个货架期内保持惰性是一个重要的标准。然而，根据活性药物和辅料在化学结构上的功能，它们可能会发生相互作用。众所周知，美拉德反应会在高温下发生在伯胺和乳糖之间，产生棕色色素。美拉德反应的反应性可能会因浓度以及其他条件而异。在商业上，有些产品的活性药物成分是伯胺，并且含有不到 75%的乳糖以及非活性辅料。在大约 2 年的环境条件下的货架期内，该产品不会发生美拉德反应。然而，当同一类型的产品含有超过 95%的乳糖作为辅料时，尽管在最初的一年中没有可见的变化，但仍有可能发生相互作用。因此，本监管说明讨论了已知药物-辅料相互作用的不同因素，并结合案例研究提供了一个概述，说明除了温度和湿度之外，乳糖在药物产品中的浓度在美拉德反应中是很重要的。
