title: Protein adsorption and excipient effects on kinetic stability of silicone oil emulsions.
abstract: The effect of silicone oil on the stability of therapeutic protein formulations is of concern in the biopharmaceutical industry as more proteins are stored and delivered in prefilled syringes. Prefilled syringes provide convenience for medical professionals and patients, but prolonged exposure of proteins to silicone oil within prefilled syringes may be problematic. In this study, we characterize systems of silicone oil-in-aqueous buffer emulsions and model proteins in formulations containing surfactant, sodium chloride, or sucrose. For each of the formulations studied, silicone oil-induced loss of soluble protein, likely through protein adsorption onto the silicone oil droplet surface. Excipient addition affected both protein adsorption and emulsion stability. Addition of surfactant stabilized emulsions but decreased protein adsorption to silicone oil microdroplets. In contrast, addition of sodium chloride increased protein adsorption and decreased emulsion stability. Silicone oil droplets with adsorbed lysozyme rapidly agglomerated and creamed out of suspension. This decrease in the kinetic stability of the emulsion is ascribed to surface charge neutralization and a bridging flocculation phenomenon and illustrates the need to investigate not only the effects of silicone oil on protein stability, but also the effects of protein formulation variables on emulsion stability.
authors.affiliation: University of Colorado, Center for Pharmaceutical Biotechnology, Boulder, Colorado 80309, USA.
authors.forename: D Brett
authors.initials: DB
authors.lastname: Ludwig
authors.forename: John F
authors.initials: JF
authors.lastname: Carpenter
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Hamel
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Randolph
mesh_terms: D000069594:Abatacept; D000327:Adsorption; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized; D002417:Cattle; D002645:Chickens; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D018796:Immunoconjugates / Q000737:chemistry; D007700:Kinetics; D009113:Muramidase / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012827:Silicone Oils / Q000737:chemistry*; D012995:Solubility; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004655:Emulsions; D005079:Excipients; D018796:Immunoconjugates; D011506:Proteins; D012827:Silicone Oils; D012710:Serum Albumin, Bovine; D000069594:Abatacept; D009113:Muramidase; D000068878:Trastuzumab