Antioxidants, Chelating Agents, and Sequestrants

The oxidation of an API in an oral liquid formulation can be difficult to control due to the trace amounts of impurities, which may be present from the API or excipient vendor, and oxidation and photolysis have relatively low activation energies (2-12 Kcal/mol) compared to solvolysis, dehydration, and polymorphic transformations (10-56 Kcal/mol) (Table 11) (10). 

BHA Antioxidant (0.01% w/v) Prevents oxidation of fats and oils and is frequently used in combination with BHT or citric acid. Trace quantities of metals and exposure to light cause discoloration and loss of activity 

EDTA Chelates alkaline earth and heavy metals 0.005-0.01% w/v antimicrobial activity synergy Often used in combination with other antimicrobial preservatives, and other antioxidants based on their synergy 

Malic acid Antioxidant, buffering agent, flavoring agent, chelating agent The powder form has a strongly acid taste and is freely soluble in ethanol and water. However, aqueous solutions are mildly corrosive to carbon steels 

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