title: Silicone Migration From Baked-on Silicone Layers. Particle Characterization in Placebo and Protein Solutions.
abstract: A significant number of therapeutic proteins are marketed as pre-filled syringes or other drug/device combination products and have been safely used in these formats for years. Silicone oil, which is used as lubricant, can migrate into the drug product and may interact with therapeutic proteins. In this study, particles in the size range of 0.2-5 μm and ≥1 μm as determined by resonant mass measurement and micro-flow imaging/light obscuration, respectively, resulted from silicone sloughing off the container barrel after agitation. The degree of droplet formation correlated well with the applied baked-on silicone levels of 13 μg and 94 μg per cartridge. Silicone migration was comparable in placebo, 2 mg/mL and 33 mg/mL IgG1 formulations containing 0.04% (w/v) polysorbate 20. Headspace substantially increased the formation of silicone droplets during agitation. The highest particle concentrations reached, however, were still very low compared to numbers described for spray-on siliconized containers. When applying adequate baked-on silicone levels below 100 μg, bake-on siliconization efficiently limits silicone migration into the drug product without compromising device functionality.
authors: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, München 81377, Germany.
authors: Stefanie
authors: S
authors: Funke
authors: F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), Basel 4070, Switzerland.
authors: Julia
authors: J
authors: Matilainen
authors: F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), Basel 4070, Switzerland.
authors: Heiko
authors: H
authors: Nalenz
authors: F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), Basel 4070, Switzerland.
authors: Karoline
authors: K
authors: Bechtold-Peters
authors: F. Hoffmann-La Roche Ltd., Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), Basel 4070, Switzerland.
authors: Hanns-Christian
authors: HC
authors: Mahler
authors: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, München 81377, Germany. Electronic address: Wolfgang.Friess@lrz.uni-muenchen.de.
authors: Wolfgang
authors: W
authors: Friess
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D007074:Immunoglobulin G / Q000032:analysis / Q000737:chemistry*; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000737:chemistry; D011108:Polymers / Q000032:analysis / Q000737:chemistry; D012828:Silicones / Q000032:analysis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013450:Sulfones / Q000032:analysis / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019999:Pharmaceutical Solutions; D011108:Polymers; D012828:Silicones; D013450:Sulfones; C022840:polyether sulfone
keywords: IgG antibody; biopharmaceutical characterization; injectors; light scattering (dynamic); materials science; ophthalmic drug delivery; particle size; protein formulation; proteins; surfactants