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Specific interactions in high concentration antibody solutions resulting in high viscosity

Sandeep Yadav1, Jun Liu, Steven J Shire

  • 1Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.

Journal of Pharmaceutical Sciences
|August 26, 2009
PubMed

Insights

Monoclonal antibody solutions exhibit self-association due to electrostatic interactions, particularly at pH 6.0. These findings are crucial for understanding antibody behavior in high-concentration formulations.

Area of Science:

  • Biochemistry
  • Materials Science
  • Physical Chemistry

Background:

  • High concentration monoclonal antibody (MAb) solutions can exhibit complex self-associating behavior.
  • Understanding these interactions is critical for formulation development and therapeutic efficacy.

Purpose of the Study:

  • To investigate the self-associating behavior of a specific monoclonal antibody (MAb1) at high concentrations and pH 6.0.
  • To elucidate the electrostatic and physicochemical factors driving these interactions.

Main Methods:

  • Zeta potential measurements across a pH range (4.0-9.0).
  • Dynamic light scattering (DLS) to determine the interaction parameter (k(D)).
  • Rheology analysis using an ultrasonic shear rheometer.

Main Results:

  • Lower net molecular charges observed at pH 6.0 and 7.0, with a point of zero charge at pH 6.7.
  • DLS indicated attractive interactions (k(D)) between pH 5.0-8.0, confirmed as electrostatic via ionic strength studies.
  • Rheology showed a high storage modulus (G') and sharp increase at high concentrations for MAb1, indicative of strong attractive interactions.

Conclusions:

  • Strong attractive interactions in MAb1 solutions at pH 6.0 are attributed to charge-charge and charge-dipole interactions in the Fab regions.
  • The observed self-association and pH-dependent rheological profile are explained by these specific surface interactions.

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