Effects of conformation on the chemical stability of pharmaceutically relevant polypeptides.

Abstract

Control of chemical instability in protein pharmaceuticals continues to be a critical issue in developing stable formulations. While the effects of pH, buffer composition, ionic strength and temperature remain the most effective methods for controlling hydrolysis and oxidation reactions, it appears that conformational control may also be important. Addition of excipients to maintain native structure and reduce the propensity of the protein to denature and/or aggregate is already a central theme in stabilizing proteins (Arakawa et al., 1993). The same additives have now been found to slow both deamidation and oxidation, whether in solution or in the solid state. What is emerging is an additional approach for producing protein pharmaceuticals that maintain native structure and activity during long-term storage.