title: Characterization of the initial level and migration of silicone oil lubricant in empty prefilled syringes for biologics using infrared spectroscopy.
abstract: Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals.
  Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals.
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, MD; jaredsbee@gmail.com.
authors.forename: Jared S
authors.initials: JS
authors.lastname: Bee
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Frey
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Urooj
authors.initials: U
authors.lastname: Javed
authors.affiliation: Drug Delivery & Devices, MedImmune, Gaithersburg, MD; and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chung
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Marta L
authors.initials: ML
authors.lastname: Corcoran
authors.affiliation: Drug Delivery & Devices, MedImmune, Gaithersburg, MD; and.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Roussel
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Stephan O
authors.initials: SO
authors.lastname: Krause
authors.affiliation: Analytical Biotechnology, MedImmune, Gaithersburg, MD;
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Cash
authors.affiliation: Formulation Sciences, MedImmune, Gaithersburg, MD;
authors.forename: Steven M
authors.initials: SM
authors.lastname: Bishop
authors.affiliation: Protein Pharmaceutical Development, Biogen Idec Inc., Boston, MA.
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Dimitrova
mesh_terms: D001688:Biological Products / Q000032:analysis*; D001702:Biopharmaceutics / Q000379:methods* / Q000592:standards; D004340:Drug Contamination; D004349:Drug Packaging; D004356:Drug Storage; D005898:Glass; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D016014:Linear Models; D054327:Lubricants / Q000032:analysis*; D009038:Motion; D012015:Reference Standards; D015203:Reproducibility of Results; D012827:Silicone Oils / Q000032:analysis*; D017550:Spectroscopy, Fourier Transform Infrared / Q000592:standards; D013594:Syringes; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D013997:Time Factors
chemical_list: D001688:Biological Products; D054327:Lubricants; D012827:Silicone Oils
keywords: Device; Infrared spectroscopy; Prefilled syringe; Silicone oil