Review of the physicochemical methods applied in the investigation of the maillard reaction in pharmaceutical preparations

摘要

In recent years there has been an increasing interest in the study of drug-excipient interactions in pharmaceutical dosage forms. Maillard reaction is one of the most important and well known drug-excipient interactions which is studied by many researchers in drugs containing at least one amine functional group. This article reviews the physicochemical methods in the evaluation of the Maillard reaction in various drug molecules and discusses about the advantages and drawbacks of the methods as well as their specific field of application for various drugs from 1993 to 2019 based on Scopus database search results. It can be concluded that the main documentations to prove this reaction is mass results for even reaction mixtures and NMR for purified adducts. DSC remains as a screening tool and cannot prove the reaction and only shows the possible incompatibility. FTIR is another complementary method to show the formation of new functional groups via the Maillard reaction when the reaction is well progressed. HPLC coupled with PDA or mass detector gives the most acceptable results. Some other methods such a Raman Confocal Microscopy can add visualization to track the Raman changes via reaction and can prove the reaction subsequently via a very simple but expensive technique.