title: Effects of submicron particles on formation of micron-sized particles during long-term storage of an interferon-β-1a solution.
abstract: We present evidence that homogeneous submicron particles can influence the growth rate of larger particles upon long-term storage in a temperature-dependent manner. Interferon-beta-1a was thermally stressed at 50°C for 6 h and characterized using nanoparticle tracking analysis (NTA), microflow digital imaging (MFI), and circular dichroism (CD) spectroscopy. This study showed selective formation of submicron particles exhibiting a perturbed protein conformation. These thermally induced submicron particles were spiked into an unstressed solution at three levels, and then monitored for micron-sized particle formation upon storage at 5°C and 25°C for 12 months. The resulting particle growth effects were temperature dependent. NTA and MFI results at 5°C showed little evidence that initial submicron particle levels impacted particle growth across the range ~0.03-25 μm. In contrast, MFI results at 25°C indicated that particle growth in the 1-10 μm size range correlated strongly with initial submicron particle levels, and particle counts in the 10-25 μm size range were highest after 12 months for the samples with highest initial submicron particle content.
authors.affiliation: Protein Pharmaceutical Development, Biogen Idec, Cambridge, Massachusetts 02142, USA.
authors.forename: Shujun
authors.initials: S
authors.lastname: Bai
authors.forename: Yogapriya
authors.initials: Y
authors.lastname: Murugesan
authors.forename: Milana
authors.initials: M
authors.lastname: Vlasic
authors.forename: Lori B
authors.initials: LB
authors.lastname: Karpes
authors.forename: Mark L
authors.initials: ML
authors.lastname: Brader
mesh_terms: D004356:Drug Storage / Q000379:methods; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000737:chemistry*; D008861:Microsomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D019999:Pharmaceutical Solutions; D013997:Time Factors
chemical_list: D019999:Pharmaceutical Solutions; D016899:Interferon-beta; D000068556:Interferon beta-1a