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Surfactant Effects on Particle Generation in Antibody Formulations in Pre-filled Syringes

Authors :
Daniel K. Schwartz
Alana Gerhardt
Theodore W. Randolph
Bao H. Nguyen
John F. Carpenter
Aaron C. McUmber
Rachael Lewus
Source :
Journal of Pharmaceutical Sciences. 104:4056-4064
Publication Year :
2015
Publisher :
Elsevier BV, 2015.

Abstract

Protein aggregation and particle formation have been observed when protein solutions contact hydrophobic interfaces, and it has been suggested that this undesirable phenomenon may be initiated by interfacial adsorption and subsequent gelation of the protein. The addition of surfactants, such as polysorbate 20, to protein formulations has been proposed as a way to reduce protein adsorption at silicone oil-water interfaces and mitigate the production of aggregates and particles. In an accelerated stability study, monoclonal antibody formulations containing varying concentrations of polysorbate 20 were incubated and agitated in pre-filled glass syringes (PFS), exposing the protein to silicone oil-water interfaces at the siliconized syringe walls, air-water interfaces, and agitation stress. Following agitation in siliconized syringes that contained an air bubble, lower particle concentrations were measured in the surfactant-containing antibody formulations than in surfactant-free formulations. Polysorbate 20 reduced particle formation when added at concentrations above or below the critical micelle concentration (CMC). The ability of polysorbate 20 to decrease particle generation in PFS corresponded with its ability to inhibit gelation of the adsorbed protein layer, which was assessed by measuring the interfacial diffusion of individual antibody molecules at the silicone oil-water interface using total internal reflectance fluorescence (TIRF) microscopy with single-molecule tracking.

Details

ISSN :
00223549
Volume :
104
Database :
OpenAIRE
Journal :
Journal of Pharmaceutical Sciences
Accession number :
edsair.doi.dedup.....b4f2a743e9e4e8cf176309b9e5cb7dc5
Full Text :
https://doi.org/10.1002/jps.24654