Impact of Buffer, Protein Concentration and Sucrose Addition on the Aggregation and Particle Formation during Freezing and Thawing.
Impact of Buffer, Protein Concentration and Sucrose Addition on the Aggregation and Particle Formation during Freezing and Thawing.
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DOI：
10.1007/s11095-018-2378-5
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发表时间：
2018-03-19
影响因子：
3.7
通讯作者：
Loerting T
中科院分区：
文献类型：
--
作者：
Hauptmann A;Podgoršek K;Kuzman D;Srčič S;Hoelzl G;Loerting T
本研究探讨了冷冻和解冻对治疗性单抗(MAb)溶液和相应的缓冲制剂的影响。研究了不同冻融速率、不同缓冲液配方和不同蛋白质浓度下的颗粒形成、结晶行为、形态变化和冷冻浓缩效应。研究了在受控和非受控温度速率下进行多次冷冻/解冻(FT)循环对mAb溶液颗粒形成的影响。用差示扫描量热法分析了样品的物理化学性质，而用冷冻显微镜测量了样品的形貌变化。用微流成像、阿基米德和动态光散射研究了颗粒的形成。本研究检索的数据强调了多个FT-环造成的损害，以及需要蔗糖作为低温保护剂来防止冷结晶，特别是在蛋白质浓度较高的情况下。较低的蛋白质浓度会增加微米级颗粒的形成。冻结速率越低，颗粒直径越大，颗粒数量越少。这项研究的总体目标是更好地了解单抗溶液的冻结和解冻行为，最终目的是通过减少不需要的颗粒形成(包括蛋白质聚集体)来优化这一过程步骤。
This study addresses the effect of freezing and thawing on a therapeutic monoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryo-concentration effects were studied after varying the freezing and thawing rates, buffer formulation and protein concentration. The impact of undergoing multiple freeze/thaw (FT)-cycles at controlled and uncontrolled temperature rates on mAb solutions was investigated in terms of particle formation. Physicochemical characteristics were analysed by Differential Scanning Calorimetry whereas morphology changes are visualized by cryomicroscopy measurements. Micro Flow Imaging, Archimedes and Dynamic Light Scattering were used to investigate particle formation. Data retrieved in the present study emphasizes the damage caused by multiple FT-cyles and the need for sucrose as a cryoprotectant preventing cold-crystallization specifically at high protein concentrations. Low protein concentrations cause an increase of micron particle formation. Low freezing rates lead to a decreased particle number with increased particle diameter. The overall goal of this research is to gain a better understanding of the freezing and thawing behaviour of mAb solutions with the ultimate aim to optimize this process step by reducing the unwanted particle formation, which also includes protein aggregates.
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影响因子：
3.8
作者：
Barnard, James G.;Singh, Satish;Carpenter, John F.
通讯作者：
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影响因子：
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DOI：
10.1016/j.ejpb.2017.06.029
发表时间：
2017-10-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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