Trimethylamine N-oxide (TMAO) is a counteracting solute of benzyl alcohol for multi-dose formulation of immunoglobulin
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Add time:07/27/2019 Source:sciencedirect.com
Multi-dose formulation of biopharmaceuticals contains an antimicrobial preservative, which may facilitate aggregation of the proteins due to their hydrophobic protein binding. Here, we have investigated the effects of co-solvents on heat-induced protein aggregation in the presence of an antimicrobial preservative. Human immunoglobulin G (IgG) and benzyl alcohol were chosen because of their wide usage as a pharmaceutical protein and a preservative. Trimethylamine N-oxide (TMAO) was found to be the most effective additive in suppressing benzyl alcohol-induced IgG aggregation among the additives tested. Interestingly, TMAO was less effective in increasing the thermal-unfolding temperature of IgG than trehalose, indicating that the observed suppression of IgG aggregation by TMAO in the presence of benzyl alcohol is not simply due to its stabilization effect of the protein structure. The solubility of benzyl alcohol increased with increasing concentrations of TMAO, suggesting that the hydrophobic interaction of TMAO with benzyl alcohol is responsible for the observed aggregation suppression. Thus, TMAO may be a potential aggregation suppressor in multi-dose formulation of biopharmaceuticals.
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