کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485173 | 1114347 | 2013 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Frozen-State Storage Stability of a Monoclonal Antibody: Aggregation is Impacted by Freezing Rate and Solute Distribution
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Frozen-State Storage Stability of a Monoclonal Antibody: Aggregation is Impacted by Freezing Rate and Solute Distribution Frozen-State Storage Stability of a Monoclonal Antibody: Aggregation is Impacted by Freezing Rate and Solute Distribution](/preview/png/2485173.png)
چکیده انگلیسی
Freezing of protein solutions perturbs protein conformation, potentially leading to aggregate formation during long-term storage in the frozen state. Macroscopic protein concentration profiles in small cylindrical vessels were determined for a monoclonal antibody frozen in a trehalose-based formulation for various freezing protocols. Slow cooling rates led to concentration differences between outer edges of the tank and the center, up to twice the initial concentration. Fast cooling rates resulted in much smaller differences in protein distribution, likely due to the formation of dendritic ice, which traps solutes in micropockets, limiting their transport by convection and diffusion. Analysis of protein stability after more than 6 months storage at either â 10°C or -20°C [above glass transition temperature (Tâ²g)] or â 80°C (below Tâ²g) revealed that aggregation correlated with the cooling rate. Slow-cooled vessels stored above Tâ²g exhibited increased aggregation with time. In contrast, fast-cooled vessels and those stored below Tâ²g showed small to no increase in aggregation at any position. Rapid entrapment of protein in a solute matrix by fast freezing results in improved stability even when stored above Tâ²g.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 4, April 2013, Pages 1194-1208
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 4, April 2013, Pages 1194-1208
نویسندگان
Maria A. Miller, Miguel A. Rodrigues, Matthew A. Glass, Satish K. Singh, Keith P. Johnston, Jennifer A. Maynard,