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

  • Review Article
  • Theme: Preclinical Peptide Developability Assessment
  • Published:
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Abstract

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.

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Acknowledgments

The authors would like to acknowledge Candice Alleyne, Erika Bartholomew, Elizabeth Sander, Lee Klein, Majid Mahjour, Suzanne D’Addio, and Caroline McGregor for useful discussions around peptide developability and/or useful comments on this article. We would also like to thank Michelle Sparks Kuo and Maria Cueto for their contributions to searching literature for the article. Lastly, the authors acknowledge Michele McColgan and Marilyn Terry for their assistance making publication-quality figures and tables.

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Author notes

  1. James Cunningham

    Present address: Drug Delivery Sciences, Allergan, Irvine, California, USA

Authors and Affiliations

  1. Discovery Pharmaceutical Sciences, Merck & Co, Kenilworth, New Jersey, USA

    Annette Bak & Nathalie Toussaint

  2. Discovery Pharmaceutical Sciences, Merck & Co, Rahway, New Jersey, USA

    Dennis Leung & Andrew W. Leithead

  3. Formulation Sciences, Merck & Co, West Point, Pennsylvania, USA

    Stephanie E. Barrett

  4. Formulation Sciences, Merck & Co, West Point, Pennsylvania, USA

    Seth Forster & James Cunningham

  5. Discovery Pharmaceutical Sciences, Merck & Co, Boston, Massachusetts, USA

    Ellen C. Minnihan

  6. Formulation Sciences, Merck & Co, Summit, New Jersey, USA

    Louis S. Crocker

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  1. Annette Bak
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Correspondence to Annette Bak.

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Guest Editors: Annette Bak and Weiguo Dai

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Bak, A., Leung, D., Barrett, S.E. et al. Physicochemical and Formulation Developability Assessment for Therapeutic Peptide Delivery—A Primer. AAPS J 17, 144–155 (2015). https://doi.org/10.1208/s12248-014-9688-2

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