Formulation Development, Eli Lilly and Company, 59-61 ImClone Drive, Branchburg, NJ, 08876, USA.
AAPS PharmSciTech. 2018 Jan;19(1):79-92. doi: 10.1208/s12249-017-0845-7. Epub 2017 Aug 2.
The purpose of this work was to evaluate the effect of commonly used surfactants (at 0.01% w/v concentration) on mechanical, thermal, and photostability of a monoclonal antibody (MAb1) of IgG1 sub-class and to evaluate the minimum concentration of surfactant (Polysorbate 80) required in protecting MAb1 from mechanical stress. Surfactants evaluated were non-ionic surfactants, Polysorbate 80, Polysorbate 20, Pluronic F-68 (polyoxyethylene-polyoxypropylene block polymer), Brij 35 (polyoxyethylene lauryl ether), Triton X-100, and an anionic surfactant, Caprylic acid (1-Heptanecarboxylic acid). After evaluating effect of surfactants and determining stabilizing effect of Polysorbate 80 against mechanical stress without compromising thermal and photostability of MAb1, the minimum concentration of Polysorbate 80 required for mechanical stability was further examined. Polysorbate 80 concentration was varied from 0 to 0.02%. Mechanical stability was evaluated by agitation of MAb1 at 300 rotations per minute at room temperature for 72 h. Samples were analyzed for purity by SEC-HPLC, turbidity by absorbance at 350 nm, visible particles by visual inspection, and sub-visible particles by light obscuration technique on a particle analyzer. All non-ionic surfactants tested showed a similar effect in protecting against mechanical stress and did not exhibit any significant negative effect on thermal and photostability. However, Caprylic acid had a slightly negative effect on mechanical and photostability when compared to the non-ionic surfactants or sample without surfactant. This work demonstrated that polysorbate 80 is better than other surfactants tested and that a concentration of at least 0.005% (w/v) Polysorbate 80 is needed to protect MAb1 against mechanical stress.
这项工作的目的是评估常用表面活性剂（浓度为 0.01%w/v）对单克隆抗体（MAb1）的机械、热和光稳定性的影响，并评估保护 MAb1 免受机械应力所需的表面活性剂（聚山梨酯 80）的最小浓度。评估的表面活性剂是非离子表面活性剂，聚山梨酯 80、聚山梨酯 20、泊洛沙姆 F-68（聚氧乙烯-聚氧丙烯嵌段聚合物）、Brij 35（聚氧乙烯月桂醚）、吐温 X-100 和阴离子表面活性剂辛酸（1-庚酸）。在评估表面活性剂的作用并确定聚山梨酯 80 对机械应激的稳定作用而不影响 MAb1 的热和光稳定性之后，进一步研究了机械稳定性所需的聚山梨酯 80 的最小浓度。聚山梨酯 80 的浓度从 0 变化到 0.02%。通过在室温下以 300 转/分钟的速度搅拌 MAb1 72 小时来评估机械稳定性。通过 SEC-HPLC 分析纯度，通过在 350nm 处的吸光度分析浊度，通过目视检查可见颗粒，通过光遮挡技术在粒子分析仪上检查亚可见颗粒。所有测试的非离子表面活性剂都表现出相似的保护作用，防止机械应激，并且对热和光稳定性没有任何显著的负面影响。然而，与非离子表面活性剂或无表面活性剂的样品相比，辛酸对机械和光稳定性有轻微的负面影响。这项工作表明，聚山梨酯 80 优于测试的其他表面活性剂，并且需要至少 0.005%（w/v）的聚山梨酯 80 浓度来保护 MAb1 免受机械应力。
