Albinterferon α2b Adsorption to Silicone Oil–Water Interfaces: Effects on Protein Conformation, Aggregation, and Subvisible Particle Formation
| Autor: | Angela W. Blake-Haskins, Kristin B. O'berry, Pinaki Basu, Theodore W. Randolph, John F. Carpenter |
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| Rok vydání: | 2014 |
| Předmět: |
Protein Conformation
Chemistry Pharmaceutical Pharmaceutical Science Excipient Buffers Sodium Chloride complex mixtures Polyvinyl alcohol Fluorescence chemistry.chemical_compound Adsorption Silicone Albumins Electrochemistry medicine Silicone Oils Particle Size Lubricant Chromatography High Pressure Liquid Acrylamides Chromatography Tryptophan technology industry and agriculture Interferon-alpha Water Silicone oil Albinterferon chemistry Particle Emulsions Particulate Matter Algorithms medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 103:427-436 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.23821 |
| Popis: | 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 α2b , to evaluate protein aggregation and particle formation in the presence of silicone oil microdroplets or immobilized silicone interfaces. Tertiary structure of albinterferon α2b adsorbed on silicone oil microdroplets was perturbed in a formulation containing only buffer. In contrast, native-like tertiary structure was retained for albinterferon α2b adsorbed on silicone oil microdroplets in 300 mM sodium chloride or 300 mM sucrose formulations. Agitation of albinterferon α2b samples in the presence of silicone oil droplets or siliconized beads, respectively, caused albinterferon α2b aggregation and subvisible particle formation in formulations containing buffer or 300 mM sucrose. Adsorption of albinterferon α2b 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. |
| Databáze: | OpenAIRE |
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