Solid‐state chemical stability of proteins and peptides

1999/05/01 by M.C. Lai, M. C. Lai, E.M. Topp +1 · 4 citations
Biochemistry, Genetics and Molecular Biology · Pharmacology, Toxicology and Pharmaceutics · #Protein purification and stability #Drug Solubulity and Delivery Systems #Advanced Drug Delivery Systems

paper · doi:10.1021/js980374e

Abstract

Peptide and protein drugs are often formulated in the solid-state to provide stabilization during storage. However, reactions can occur in the solid-state, leading to degradation and inactivation of these agents. This review summarizes the major chemical reactions affecting proteins and peptides in the solid-state: deamidation, peptide bond cleavage, oxidation, the Maillard reaction, beta-elimination, and dimerization/aggregation. Physical and chemical factors influencing these reactions are also discussed. These include temperature, moisture content, excipients, and the physical state of the formulation (amorphous vs crystalline). The review is intended to serve as an aid for those involved in formulation, and to stimulate further research on the determinants of peptide and protein reactivity in the solid-state.

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