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Effect of Sugar Molecules on the Viscosity of High Concentration Monoclonal Antibody Solutions

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ABSTRACT

Purpose

To assess the effect of sugar molecules on solution viscosity at high protein concentrations.

Methods

A high throughput dynamic light scattering method was used to measure the viscosity of monoclonal antibody solutions. The effects of protein concentration, type of sugar molecule (trehalose, sucrose, sorbitol, glucose, fructose, xylose and galactose), temperature and ionic strength were evaluated. Differential scanning fluorimetry was used to reveal the effect of the same sugars on protein stability and to provide insight into the mechanism by which sugars increase viscosity.

Results

The addition of all seven types of sugar molecules studied result in a significant increase in viscosity of high concentration monoclonal antibody solutions. Similar effects of sugars were observed in the two mAbs examined; viscosity could be reduced by increasing the ionic strength or temperature. The effect by sugars was enhanced at higher protein concentrations.

Conclusions

Disaccharides have a greater effect on the solution viscosity at high protein concentrations compared to monosaccharides. The effect may be explained by commonly accepted mechanisms of interactions between sugar and protein molecules in solution.

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Abbreviations

cP:

centipoise

DLS:

dynamic light scattering

DSF:

differential scanning fluorimetry

Igg:

Immunoglobulin G

mAb:

monoclonal antibody

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ACKNOWLEDGMENTS

The authors are grateful towards Fan Zhang and Dr. Jeremy Guo for supplying research materials. The authors would also like to thank Drs. R. Matthew Fesinmeyer, Gerald Becker, Linda Narhi, David Brems, and Michael Treuheit for critical reviews and fruitful discussions.

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Authors and Affiliations

  1. Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA

    Feng He, Christopher E. Woods & Vladimir I. Razinkov

  2. Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA

    Jennifer R. Litowski, Lauren A. Roschen, Himanshu S. Gadgil & Bruce A. Kerwin

  3. AW2/D3152, 1201 Amgen Court West, Seattle, Washington, 98119, USA

    Feng He & Bruce A. Kerwin

Authors
  1. Feng He
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  2. Christopher E. Woods
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  3. Jennifer R. Litowski
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  4. Lauren A. Roschen
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  5. Himanshu S. Gadgil
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  6. Vladimir I. Razinkov
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  7. Bruce A. Kerwin
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Correspondence to Feng He or Bruce A. Kerwin.

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He, F., Woods, C.E., Litowski, J.R. et al. Effect of Sugar Molecules on the Viscosity of High Concentration Monoclonal Antibody Solutions. Pharm Res 28, 1552–1560 (2011). https://doi.org/10.1007/s11095-011-0388-7

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  • DOI: https://doi.org/10.1007/s11095-011-0388-7

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