Format

Send to

Choose Destination
See comment in PubMed Commons below
J Pharm Sci. 2013 Apr;102(4):1194-208. doi: 10.1002/jps.23473. Epub 2013 Feb 8.

Frozen-state storage stability of a monoclonal antibody: aggregation is impacted by freezing rate and solute distribution.

Author information

1
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.

Abstract

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 -10°C or -20°C [above glass transition temperature (T'g )] or -80°C (below T'g ) revealed that aggregation correlated with the cooling rate. Slow-cooled vessels stored above T'g exhibited increased aggregation with time. In contrast, fast-cooled vessels and those stored below T'g 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 T'g . © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1194-1208, 2013.

PMID:
23400717
DOI:
10.1002/jps.23473
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center