Drying for Stabilization of Protein Formulations

Drying can significantly improve the stability of protein drugs compared with liquid formulation. This chapter discusses mechanisms of protein stabilization in liquid and dried formulations as well as the corresponding analytical methods. It summarizes the impact of the drying process itself on protein stability. Almost exclusively, freeze drying is employed for protein drug products for this purpose. However, chemical instability like formation of disulfide bonds, oxidation, deamidation, or glycation and physical instability such as conformational instability or aggregation also occur in the dried state. In contrast to freeze drying, spray drying is a one-stage process. An enormous air-liquid interface is generated, which triggers protein adsorption and aggregation. Spray drying at higher temperature is performed, which can be critical for the conformational stability of the protein.