Article

Pharmaceutical Research

, Volume 20, Issue 9, pp 1325-1336

First online:

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

  • Eva Y. ChiAffiliated withDepartment of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, University of Colorado
  • , Sampathkumar KrishnanAffiliated withDepartment of Pharmaceutics and Drug Delivery, Amgen Inc.
  • , Theodore W. RandolphAffiliated withDepartment of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, University of Colorado
  • , John F. CarpenterAffiliated withDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center Email author 

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Abstract

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