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Stability of lyophilized sucrose formulations of an IgG1: subvisible particle formation.

Authors
  • Davis, Janice M1
  • Zhang, Ning
  • Payne, Robert W
  • Murphy, Brian M
  • Abdul-Fattah, Ahmad M
  • Matsuura, James E
  • Herman, Alan C
  • Manning, Mark Cornell
  • 1 Althea Technologies, San Diego, CA, USA.
Type
Published Article
Journal
Pharmaceutical development and technology
Publication Date
Jan 01, 2013
Volume
18
Issue
4
Pages
883–896
Identifiers
DOI: 10.3109/10837450.2012.705295
PMID: 22813478
Source
Medline
License
Unknown

Abstract

Eight lyophilized formulations of a IgG1 monoclonal antibody (MAb) were prepared containing increasing levels of sucrose. In addition, three of the formulations had sorbitol added at a level of 5% w/w relative to sucrose. The samples were stored for up to 4 weeks at 40°C, which is well below the Tg. Upon reconstitution, the levels of subvisible particles were measured using microflow imaging (MFI). The formulation containing no sucrose contained exceedingly high levels of subvisible particles, accounting for as much as 25% of the weight of the protein. Addition of sucrose markedly decreased the number of subvisible particles, with the maximal sucrose:protein weight ratio being 2:1 (the highest level tested). Addition of sorbitol further decreased subvisible particle levels, even for formulations where the sucrose:protein ratio was relatively high. This suggests that even small amounts of a plasticizer like sorbitol can improve the storage stability of a lyophilized antibody formulation, probably by dampening β-relaxations within the amorphous glass.

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