A Review on Forced Degradation Strategies to Establish the Stability of Therapeutic Peptide Formulations

Abstract

Peptides are small polymers composed of 40 or fewer amino acids and are an increasingly important class of drugs. Therapeutic peptides are less immunogenic and more economical than biologics while offering greater safety, selectivity, efficacy, and specificity than small molecule drugs. Despite this, they are challenging to mold in a stable formulation due to their susceptibility to degradation. By understanding the degradation behavior of such peptide drugs, researchers and pharmaceutical manufacturers can design safe, effective, and stable peptide formulations. From a scientific standpoint, forced degradation studies are an indispensable tool to forecast the stability of any molecule during its development phase. Being structurally diverse, the degradation of peptide drugs is different from the small molecules. This review provides a practical summary of strategies adopted to perform the stress stability testing for different peptide therapeutics including a selection of stress conditions, degradation products formed, and an analytical methodology used for the characterization of degradation products. Hence, it will help in developing a protocol for performing forced degradation studies on peptide therapeutics of interest. In-depth discussions of the different peptide degradation mechanisms are also included, along with preventive measures. The information presented here in the form of case studies on the degradation profile of existing peptide drugs will help in designing more resistant peptide drugs by chemical modifications, as well as aid in the advancement of generic peptide drug product development. In brief, this review presents the way of controlling peptide degradation from synthesis to formulation development based on their constituted amino acids.