In this study, we screened 759 combinations of natural saccharides and amino compounds for their efficacy as pharmaceutical excipients. We found that aqueous solutions containing 1 M trehalose and 0.0625–1 M of sodium glutamate inhibited aggregate formation and synergistically protected both murine mAbs and therapeutic humanized antibody (Ixekizumab) from thermal loss of immunoreactivity at 73°C, when compared with each single constituent alone. In addition, they exhibited protection against thermal denaturation of lactate dehydrogenase at 70°C. Total concentrations of trehalose and sodium glutamate needed to be no less than 0.8 M to give synergistic stabilizing effects on proteins under our set thermal conditions. Furthermore, the aqueous solutions synergized with polysorbate 80 or polysorbate 20 to protect mAbs against thermal loss of immunoreactivity. Our results provide novel insights into the application of saccharides and amino acids in combination as stable storage solutions for therapeutic antibodies and diagnostic enzymes.
Learning Objectives:
Recognize that environmentally friendly aqueous solutions containing trehalose and sodium glutamate at total concentrations of 1.0 M or higher synergistically stabilize a variety of proteins
Recognize the protein stabilizing effect of the solutions is synergistically enhanced when used in combination with polysorbate 80 or 20
