Understanding acid-base relationships and the change in ionization state during freezing and drying informs selection of excipients and formulation composition Changes in the acid-base relationships can destabilize protein mols. either directly, via specific acid-base catalysis, or indirectly, by changing the ionization state of the protein and thus making it potentially more susceptible to both phys. (e.g. aggregation) and chem. (e.g. oxidation) degradation pathways. During freeze-drying or spray-drying processes, proteins are exposed to a variety of interfaces such as air-water, ice-solution, glass-solution, etc. It is well established with numerous proteins that encounters with various interfaces likely result in some degree of protein adsorption. Although stabilization of amorphous formulations is oftentimes an empirical exercise, understanding the basic principles of mol. mobility will help a formulator rationally develop stable solid-state formulations.