Pharmaceutical Research

, Volume 29, Issue 11, pp 3102–3109 | Cite as

Structure-Activity Relationship for Hydrophobic Salts as Viscosity-Lowering Excipients for Concentrated Solutions of Monoclonal Antibodies

  • Zheng Guo
  • Alvin Chen
  • Roger A. Nassar
  • Bernhard Helk
  • Claudia Mueller
  • Yu Tang
  • Kapil Gupta
  • Alexander M. Klibanov
Research Paper



To discover, elucidate the structure-activity relationship (SAR), and explore the mechanism of action of excipients able to drastically lower the viscosities of concentrated aqueous solutions of humanized monoclonal antibodies (MAbs).


Salts prepared from hydrophobic cations and anions were dissolved into humanized MAbs solutions. Viscosities of the resulting solutions were measured as a function of the nature and concentration of the salts and MAbs.


Even at moderate concentrations, some of the salts prepared herein were found to reduce over 10-fold the viscosities of concentrated aqueous solutions of several MAbs at room temperature.


To be potent viscosity-lowering excipients, the ionic constituents of the salts must be hydrophobic, bulky, and aliphatic. A mechanistic hypothesis explaining the observed salt effects on MAb solutions’ viscosities was proposed and verified.


excipients monoclonal antibodies proteins rheology salts structure-activity relationship (SAR) viscosity 



Chinese hamster ovary


monoclonal antibody


structure-activity relationship




standard deviation



This study was financially supported by Novartis AG, which also kindly supplied the humanized MAbs used by us.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Zheng Guo
    • 1
    • 3
  • Alvin Chen
    • 2
  • Roger A. Nassar
    • 1
  • Bernhard Helk
    • 4
  • Claudia Mueller
    • 4
  • Yu Tang
    • 5
  • Kapil Gupta
    • 5
  • Alexander M. Klibanov
    • 1
    • 2
  1. 1.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Engineering, Faculty of Science and TechnologyAarhus UniversityAarhus CDenmark
  4. 4.Novartis Pharma AGBaselSwitzerland
  5. 5.Novartis Institutes for BioMedical Research, Inc.CambridgeUSA

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