Peptide Stability in Solids and Solutions

A discussion of the factors influencing peptide stability illustrates the challenges of formulation and shelf‐life prediction which face biotechnologists. The activation energies of peptide degradation vary with pH and moisture content. Peptide degradation rates are influenced by both buffer type and concentration. Lyophilization results in an increase in buffer concentration which also enhances peptide degradation in low‐moisture solids. Small peptides have degradation rates that depend upon water activity rather than upon mobility limitations associated with the state of the system. The pH−rate profiles for peptide degradation in solution and solids are quite different. Dehydration and partial rehydration change the pH of reduced‐moisture solids, which change both the rates and mechanisms of degradation. The properties of the peptide and the system as well as potential interactions between the two need to be identified to maximize peptide stability. In addition, solution data cannot be used to predict the shelf life of reduced‐moisture solids.