期刊
PHARMACEUTICAL RESEARCH
卷 35, 期 5, 页码 -出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-018-2378-5
关键词
buffer and mAb formulation; cryomicroscopy; freezing; particle formation; thawing
资金
- Austrian Science Fund (FWF)
- Austrian Science Fund FWF [I1392]
- Sandoz GmbH, Austria/Lek Menges, Slovenia
- Austrian Science Fund (FWF) [I1392] Funding Source: Austrian Science Fund (FWF)
Purpose This study addresses the effect of freezing and thawing on a therapeuticmonoclonal antibody (mAb) solution and the corresponding buffer formulation. Particle formation, crystallization behaviour, morphology changes and cryoconcentration 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. Methods 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. Results Data retrieved in the present study emphasizes the damage caused by multiple FT-cyles and the need for sucrose as a cryoprotectant preventing coldcrystallization 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. Conclusion 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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