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Updated: Apr 10, 2026
Measurement of Particle Size Distribution in Turbid Solutions by Dynamic Light Scattering Microscopy
Published on: January 9, 2017
Quantitative Correlation between Viscosity of Concentrated MAb Solutions and Particle Size Parameters Obtained from
Masakazu Fukuda1, Chifumi Moriyama2, Tadao Yamazaki2
1Production Engineering Department, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo, 115-8543, Japan. fukuda.masakazu76@chugai-pharm.co.jp.
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.
