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Pharmaceutical Research

, Volume 6, Issue 11, pp 903–918 | Cite as

Stability of Protein Pharmaceuticals

  • Mark C. Manning
  • Kamlesh Patel
  • Ronald T. Borchardt
Article

Abstract

Recombinant DNA technology has now made it possible to produce proteins for pharmaceutical applications. Consequently, proteins produced via biotechnology now comprise a significant portion of the drugs currently under development. Isolation, purification, formulation, and delivery of proteins represent significant challenges to pharmaceutical scientists, as proteins possess unique chemical and physical properties. These properties pose difficult stability problems. A summary of both chemical and physical decomposition pathways for proteins is given. Chemical instability can include proteolysis, deamidation, oxidation, racemization, and β-elimination. Physical instability refers to processes such as aggregation, precipitation, denaturation, and adsorption to surfaces. Current methodology to stabilize proteins is presented, including additives, excipients, chemical modification, and the use of site-directed mutagenesis to produce a more stable protein species.

protein stability biotechnology mutagenesis denaturation 

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Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Mark C. Manning
    • 1
  • Kamlesh Patel
    • 1
  • Ronald T. Borchardt
    • 1
  1. 1.Department of Pharmaceutical ChemistryThe University of KansasLawrence

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