Albinterferon alpha(2b) Adsorption to Silicone Oil-Water Interfaces: Effects on Protein Conformation, Aggregation, and Subvisible Particle Formation

作者：Basu Pinaki; Blake Haskins Angela W; O'Berry Kristin B; Randolph Theodore W; Carpenter John F^*

来源：Journal of Pharmaceutical Sciences, 2014, 103(2): 427-436.

DOI：10.1002/jps.23821

• protein aggregation
• particle sizing
• protein formulation
• chromatography
• imaging methods
• silicone oil
• siliconized glass beads
• adsorption
• subvisible particles
• prefilled syringes

Silicone oil used as a lubricant in prefilled syringes has the potential to induce formation of particles in protein formulations. In the current study, we used a therapeutic fusion protein, albinterferon alpha(2b), to evaluate protein aggregation and particle formation in the presence of silicone oil microdroplets or immobilized silicone interfaces. Tertiary structure of albinterferon alpha(2b) adsorbed on silicone oil microdroplets was perturbed in a formulation containing only buffer. In contrast, native-like tertiary structure was retained for albinterferon alpha(2b) adsorbed on silicone oil microdroplets in 300 mM sodium chloride or 300 mM sucrose formulations. Agitation of albinterferon alpha(2b) samples in the presence of silicone oil droplets or siliconized beads, respectively, caused albinterferon alpha(2b) aggregation and subvisible particle formation in formulations containing buffer or 300 mM sucrose. Adsorption of albinterferon alpha(2b) onto silicone oil was inhibited by addition of 0.01% (w/v) polysorbate 80, and this excipient prevented aggregation during agitation in the presence of silicone oil microdroplets. Aggregation was also reduced in the presence of 300 mM sodium chloride during agitation at least in part because of the increased conformational stability of the protein.

• 出版日期2014-2