title: Degradation pathways, analytical characterization and formulation strategies of a peptide and a protein. Calcitonine and human growth hormone in comparison.
abstract: Peptides and proteins differ from conventional chemical entities in their sensitivity to numerous environmental factors and their susceptibility to different degradation pathways. Therefore, complex analytical methodologies are necessary to characterize their molecular entity as well as to detect and quantify the possible degradation products. The formulation of these molecules for a pharmaceutical product requires stabilization by various excipients. Most of the products are brought to market as solutions or lyophilisates. In the first part, this article presents a comparison between the degradation profile of a peptide (calcitonine) and a protein (human growth hormone), in solution and as a freeze-dried product. The various analytical methods used to characterize and identify the degradation products are reviewed and discussed. The second part contains an overview of the different formulation strategies for calcitonine and human growth hormone. Finally, the different stress conditions used to obtain stability data are discussed critically. This leads on to general comments on the design of stability studies for peptide and protein drugs as pharmaceuticals taking into consideration the official guidelines.
authors.affiliation: Sandoz Pharma AG, Quality Assurance, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Cholewinski
authors.forename: B
authors.initials: B
authors.lastname: Lückel
authors.forename: H
authors.initials: H
authors.lastname: Horn
mesh_terms: D000595:Amino Acid Sequence; D002116:Calcitonin / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D019382:Human Growth Hormone / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D019382:Human Growth Hormone; D002116:Calcitonin