Structural modifications for the conversion of proteins and peptides into stable dried powder formulations: A review

The drying of biomolecules into powdered formulations has become the main form of long-term product stabilisation, allowing for the delivery of safe and efficient medicines. Stability of proteins and peptides during the drying process is paramount for product quality. Drying macromolecules with an appropriate excipient is often sufficient for product stabilisation, however there are limitations imposed on excipient use, particularly in the production of high-value biopharmaceuticals. Innovative approaches for the enhancement of protein stability during dehydration need to be further explored. In this review, we provide a brief discussion of the available drying methods and current stabilisation techniques available for proteins and peptides and review the current impact and limitations of excipient use. Alongside, we take a detailed look at the impact of post-translational modifications (PTMs) and structural mutations in drying stability of biomolecules. The structural modifications mentioned in this paper are discussed in light of published work on their impact on protein and peptide stability during commonly experienced stresses, particularly those which relate to drying processes, such as chemical, thermal and freeze-thaw. The aim of this review is to direct a research focus towards upstream modifications of proteins and peptides as a viable stabilisation approach during harsh drying processes.