Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer

• Published in: The AAPS journal Vol. 17; no. 1; pp. 144 - 155
• Main Authors: Bak, Annette, Leung, Dennis, Barrett, Stephanie E., Forster, Seth, Minnihan, Ellen C., Leithead, Andrew W., Cunningham, James, Toussaint, Nathalie, Crocker, Louis S.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.01.2015
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical - methods; Drug Administration Routes; Drug Delivery Systems; Drug Design; Humans; Patient Preference; Peptides - administration & dosage; Pharmacology/Toxicology; Pharmacy; Review; Review Article; Theme: Preclinical Peptide Developability Assessment; parenteral peptide delivery; developability; oral peptide delivery; peptide therapeutics
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-014-9688-2

Peptides are an important class of endogenous ligands that regulate key biological cascades. As such, peptides represent a promising therapeutic class with the potential to alleviate many severe disease states. Despite their therapeutic potential, peptides frequently pose drug delivery challenges to scientists. This review introduces the physicochemical, biophysical, biopharmaceutical, and formulation developability aspects of peptides pertinent to the drug discovery-to-development interface. It introduces the relevance of these properties with respect to the delivery modalities available for peptide pharmaceuticals, with the parenteral route being the most prevalent route of administration. This review also presents characterization strategies for oral delivery of peptides with the aim of illuminating developability issues with the drug candidate. A brief overview of other routes of administration, including inhaled, transdermal, and intranasal routes, is provided as these routes are generally preferred by patients over injectables. Finally, this review presents formulation techniques to mitigate some of the developability obstacles associated with peptide delivery. The authors emphasize opportunities for the thoughtful application of pharmaceutical science to the development of peptide drugs and to the general advancement of this promising class of pharmaceuticals.