Analytical & Quality Evaluation Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo, 134-8630, Japan.
Pharm Res. 2012 Feb;29(2):397-410. doi: 10.1007/s11095-011-0563-x. Epub 2011 Aug 19.
To investigate relationship between second virial coefficient B (2) and viscosity and aggregation propensity of highly concentrated monoclonal antibody (MAbs) solutions.
Intermolecular interactions of 3 MAbs solutions with varying pH were characterized according to B (2) estimated by analytical ultracentrifugation sedimentation equilibrium with initial loading concentrations <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at concentrations higher than 100 mg/mL were conducted.
B (2) of all MAb solutions depended on solution pH and have qualitative correlation with viscosity and aggregation propensity. The more negative the B (2) values, the more viscous the solution, acquiring increased propensity to aggregate. Solutions with B (2) values of ~2 × 10(-5) mL·mol/g(2) acquire similar viscosity and aggregation propensity regardless of amino acid sequences; for solutions with negative B (2) values, viscosity and aggregation propensity differed depending on sequences. Results suggest attractive intermolecular interactions represented by negative B (2) values are influenced by surface properties of individual MAbs.
B (2) can be used, within certain limitations, as an effective indicator of viscosity and aggregation propensity of highly concentrated MAb solutions.
研究第二维里系数 B（2）与高浓度单克隆抗体（MAb）溶液的粘度和聚集倾向之间的关系。
根据分析超速离心沉降平衡法估算的 B（2），用初始加载浓度 <10 mg/mL 对具有不同 pH 值的 3 种 MAb 溶液的分子间相互作用进行了表征。对高于 100 mg/mL 浓度的 MAb 溶液进行了粘度测量和稳定性评估。
所有 MAb 溶液的 B（2）均取决于溶液 pH 值，与粘度和聚集倾向具有定性相关性。B（2）值越负，溶液越粘稠，聚集倾向越大。具有 ~2×10(-5) mL·mol/g(2) B（2）值的溶液无论氨基酸序列如何，其粘度和聚集倾向都相似；对于具有负 B（2）值的溶液，粘度和聚集倾向因序列而异。结果表明，由负 B（2）值表示的分子间吸引力相互作用受单个 MAb 的表面特性影响。
B（2）可在一定限制内用作高浓度 MAb 溶液粘度和聚集倾向的有效指标。
