title: Aggregation and Particle Formation of Therapeutic Proteins in Contact With a Novel Fluoropolymer Surface Versus Siliconized Surfaces: Effects of Agitation in Vials and in Prefilled Syringes.
abstract: We examined the effects of an accelerated agitation protocol on 2 protein therapeutics, intravenous immunoglobulin (IVIG) and Avastin (bevacizumab), in contact with a novel fluoropolymer surface and more typical siliconized surfaces. The fluoropolymer surface provides "solid-phase" lubrication for the syringe plunger-obviating the need for silicone oil lubrication in prefilled syringes. We tested the 2 surfaces in a vial system and in prefilled glass syringes. We also examined the effects of 2 buffers, phosphate-buffered saline (PBS) and 0.2-M glycine, with and without the addition of polysorbate 20, on agitation-induced aggregation of IVIG. Aggregation was monitored by measuring subvisible particle formation and soluble protein loss. In both vials and syringes, protein particle formation was much lower during agitation with the fluoropolymer surface than with the siliconized surface. Also, particle formation was greater in PBS than in glycine buffer, an effect attributed to lower colloidal stability of IVIG in PBS. Polysorbate 20 in the formulation greatly inhibited protein particle formation. Overall, the fluoropolymer plunger surface in an unsiliconized glass barrel was demonstrated to be a viable solution for eliminating silicone oil droplets from prefilled syringe formulations and providing a consistent system for rationale formulation development and simplified particle analysis.
authors.affiliation: Deparment of Pharmaceutical Sciences, University of Colorado Center for Pharmaceutical Biotechnology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Teska
authors.affiliation: W.L. Gore and Associates, Gore PharmBIO Products, Elkton, Maryland 21921.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Brake
authors.affiliation: W.L. Gore and Associates, Gore PharmBIO Products, Elkton, Maryland 21921.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Tronto
authors.affiliation: Deparment of Pharmaceutical Sciences, University of Colorado Center for Pharmaceutical Biotechnology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045. Electronic address: john.carpenter@ucdenver.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: Carpenter
mesh_terms: D000068258:Bevacizumab / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004349:Drug Packaging; D005079:Excipients; D005465:Fluorocarbon Polymers / Q000737:chemistry*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D052638:Particulate Matter; D011136:Polysorbates; D066329:Protein Aggregates; D012828:Silicones / Q000737:chemistry*; D013499:Surface Properties; D013594:Syringes
chemical_list: D005079:Excipients; D005465:Fluorocarbon Polymers; D016756:Immunoglobulins, Intravenous; D052638:Particulate Matter; D011136:Polysorbates; D066329:Protein Aggregates; D012828:Silicones; D000068258:Bevacizumab
keywords: absorption; biopharmaceuticals characterization; drug delivery systems; protein aggregation; protein delivery; protein formulation