Non-Aqueous Suspensions of Antibodies are Much Less Viscous Than Equally Concentrated Aqueous Solutions
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Author(s)
Srinivasan, Charudharshini
Weight, Alisha Kessel
Bussemer, Till
Klibanov, Alexander M.
Date Issued
March 2013
Journal
Pharmaceutical Research
Publisher
Springer Science+Business Media
Citation
Srinivasan, Charudharshini, Alisha K. Weight, Till Bussemer, and Alexander M. Klibanov. “Non-Aqueous Suspensions of Antibodies Are Much Less Viscous Than Equally Concentrated Aqueous Solutions.” Pharmaceutical Research 30, no. 7 (March 30, 2013): 1749–1757.
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Author's final manuscript
Abstract
Purpose:
The aim of this study was to markedly lower the viscosities of highly concentrated protein, in particular antibody, formulations. An effective approach elaborated herein for γ-globulin and a monoclonal antibody is to replace aqueous solutions with equimolar suspensions in neat organic solvents.
Methods:
Viscosities of aqueous solutions and non-aqueous suspensions of the model protein bovine γ-globulin and a murine monoclonal antibody were examined under a variety of experimental conditions. In addition, protein particle sizes were measured using dynamic light scattering and light microscopy.
Results:
Concentrated suspensions of amorphous γ-globulin powders (up to 300 mg/mL, composed of multi-micron-sized particles) in absolute ethanol and a number of other organic solvents were found to have viscosities up to 38 times lower than the corresponding aqueous solutions. Monoclonal antibody follows the same general trend. Additionally, the higher the protein concentration and lower the temperature, the greater the viscosity benefit of a suspension over a solution.
Conclusions:
The viscosities of concentrated γ-globulin and monoclonal antibody suspensions in organic solvents are drastically reduced compared to the corresponding aqueous solutions; the magnitude of this reduction depends on the solvent, particularly its hydrogen-bonding properties.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1007/s11095-013-1017-4
