title: Cross-linked silicone coating: a novel prefilled syringe technology that reduces subvisible particles and maintains compatibility with biologics.
abstract: Prefilled syringes (PFSs) offer improvements in the delivery of drugs to patients compared with traditional vial presentations and are becoming necessities in an increasingly competitive biologics market. However, the development of a product in a PFS must take into account potential incompatibilities between the drug and the components of the syringe. One such component is silicone oil, which has previously been suggested to promote protein aggregation, loss of soluble protein, and an increase in the particulate content of injectable formulations. This study evaluated the particulate content in a model buffer system (polysorbate 80/phosphate-buffered saline) after agitation in glass syringes with a novel cross-linked silicone coating. We also evaluated the compatibility of two monoclonal antibodies with these syringes. We report that syringes with this novel coating, compared with standard siliconized syringes, exhibited reduced particle content and enhanced integrity of the lubricant layer as determined by reflectometry, optical microscopy, and time-of-flight secondary ion mass spectrometry measurements, while maintaining the desired functional properties of the syringe and the antibodies' stability profiles as determined by high-performance size-exclusion chromatography. Enhanced integrity of the lubricant coating led to significantly fewer subvisible particles in the liquid formulations, particularly after agitation stresses introduced by shipping of the syringes.
authors.affiliation: Formulation Sciences Department, MedImmune, Gaithersburg, Maryland, 20878.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Depaz
authors.forename: Tzvetelina
authors.initials: T
authors.lastname: Chevolleau
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jouffray
authors.forename: Roja
authors.initials: R
authors.lastname: Narwal
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Dimitrova
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004344:Drug Incompatibility; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D012828:Silicones / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D013594:Syringes; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D002021:Buffers; D004364:Pharmaceutical Preparations; D011136:Polysorbates; D012828:Silicones; D012965:Sodium Chloride
keywords: XSiTM; biotechnology; cross-linked silicone; formulation; injectables; prefilled syringes; protein delivery; protein formulation; silicone oil; subvisible particles