title: Colloidal Instability Fosters Agglomeration of Subvisible Particles Created by Rupture of Gels of a Monoclonal Antibody Formed at Silicone Oil-Water Interfaces.
abstract: In this study, we investigated the effect of ionic strength (1.25-231 mM) on viscoelastic interfacial gels formed by a monoclonal antibody at silicone oil-water interfaces, and the formation of subvisible particles due to rupture of these gels. Rates of gel formation and their elastic moduli did not vary significantly with ionic strength. Likewise, during gel rupture no significant effects of ionic strength were observed on particle formation and aggregation as detected by microflow imaging, resonance mass measurement, and size exclusion chromatography. Subvisible particles formed by mechanical rupturing of the gels agglomerated over time, even during quiescent incubation, due to the colloidal instability of the particles.
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: Shyam B
authors.initials: SB
authors.lastname: Mehta
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: John F
authors.initials: JF
authors.lastname: Carpenter
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309. Electronic address: theodore.randolph@colorado.edu.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Randolph
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D003102:Colloids; D005782:Gels / Q000737:chemistry*; D009994:Osmolar Concentration; D066329:Protein Aggregates; D055550:Protein Stability; D012212:Rheology; D012827:Silicone Oils / Q000737:chemistry*; D055672:Static Electricity; D013594:Syringes; D055682:Viscoelastic Substances; D014867:Water / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D003102:Colloids; D005782:Gels; D066329:Protein Aggregates; D012827:Silicone Oils; D055682:Viscoelastic Substances; D014867:Water
keywords: IgG antibody; colloid; gels; monoclonal antibody; protein formulation; proteins; rheology; salts/salt selection; stability