Pharmaceutical Research

, Volume 20, Issue 9, pp 1325–1336 | Cite as

Physical Stability of Proteins in Aqueous Solution: Mechanism and Driving Forces in Nonnative Protein Aggregation

  • Eva Y. Chi
  • Sampathkumar Krishnan
  • Theodore W. Randolph
  • John F. Carpenter


Irreversible protein aggregation is problematic in the biotechnology industry, where aggregation is encountered throughout the lifetime of a therapeutic protein, including during refolding, purification, sterilization, shipping, and storage processes. The purpose of the current review is to provide a fundamental understanding of the mechanisms by which proteins aggregate and by which varying solution conditions, such as temperature, pH, salt type, salt concentration, cosolutes, preservatives, and surfactants, affect this process.

formulation pharmaceuticals denaturation second virial coefficient conformational stability 


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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Eva Y. Chi
    • 1
  • Sampathkumar Krishnan
    • 2
  • Theodore W. Randolph
    • 1
  • John F. Carpenter
    • 3
  1. 1.Department of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111University of ColoradoBoulder
  2. 2.Department of Pharmaceutics and Drug DeliveryAmgen Inc.Thousand Oaks
  3. 3.Department of Pharmaceutical Sciences, School of PharmacyUniversity of Colorado Health Sciences CenterDenver

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