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Quantitative Correlation between Viscosity of Concentrated MAb Solutions and Particle Size Parameters Obtained from Small-Angle X-ray Scattering

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A Correction to this article was published on 24 February 2023

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Abstract

Purpose

To investigate the relationship between viscosity of concentrated MAb solutions and particle size parameters obtained from small-angle X-ray scattering (SAXS).

Methods

The viscosity of three MAb solutions (MAb1, MAb2, and MAb3; 40–200 mg/mL) was measured by electromagnetically spinning viscometer. The protein interactions of MAb solutions (at 60 mg/mL) was evaluated by SAXS. The phase behavior of 60 mg/mL MAb solutions in a low-salt buffer was observed after 1 week storage at 25°C.

Results

The MAb1 solutions exhibited the highest viscosity among the three MAbs in the buffer containing 50 mM NaCl. Viscosity of MAb1 solutions decreased with increasing temperature, increasing salt concentration, and addition of amino acids. Viscosity of MAb1 solutions was lowest in the buffer containing histidine, arginine, and aspartic acid. Particle size parameters obtained from SAXS measurements correlated very well with the viscosity of MAb solutions at 200 mg/mL. MAb1 exhibited liquid–liquid phase separation at a low salt concentration.

Conclusions

Simultaneous addition of basic and acidic amino acids effectively suppressed intermolecular attractive interactions and decreased viscosity of MAb1 solutions. SAXS can be performed using a small volume of samples; therefore, the particle size parameters obtained from SAXS at intermediate protein concentration could be used to screen for low viscosity antibodies in the early development stage.

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Change history

Abbreviations

D max app :

Apparent maximum dimension

EMS:

Electromagnetically spinning

IFT:

Indirect fourier transformation

p(r):

Pair–distance distribution function

q.s.:

quantity sufficient

R g app :

Apparent radius of gyration

SAXS:

Small-angle X-ray scattering

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Dr. Kohei Tsumoto (Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo) for thoughtful discussions. The authors also thank Akira Hayasaka, Masaru Muraoka, and Yuji Hori in the Discovery Research Department of Chugai Pharmaceutical Co., Ltd. for their support with viscosity measurements.

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Authors and Affiliations

  1. Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, 115-8543, Japan

    Masakazu Fukuda, Chifumi Moriyama, Tadao Yamazaki, Yoshimi Imaeda & Akiko Koga

Authors
  1. Masakazu Fukuda
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  2. Chifumi Moriyama
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  3. Tadao Yamazaki
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  4. Yoshimi Imaeda
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  5. Akiko Koga
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Corresponding author

Correspondence to Masakazu Fukuda.

Additional information

The original article has been corrected. The expression “I(r)” has changed to “I(q)” in an equation in page 3805. The supplementary files have been updated to remove the revision history.

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Fukuda, M., Moriyama, C., Yamazaki, T. et al. Quantitative Correlation between Viscosity of Concentrated MAb Solutions and Particle Size Parameters Obtained from Small-Angle X-ray Scattering. Pharm Res 32, 3803–3812 (2015). https://doi.org/10.1007/s11095-015-1739-6

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  • DOI: https://doi.org/10.1007/s11095-015-1739-6

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