title: Mechanistic understanding of protein-silicone oil interactions.
abstract: OBJECTIVE
  To investigate interactions between protein and silicone oil so that we can provide some mechanistic understanding of protein aggregation in silicone oil lubricated syringes and its prevention by formulation additives such as Polysorbate 80 and Poloxamer 188.
  
  
  METHODS
  Interfacial tension values of silicone oil/water interface of abatacept solutions with and without formulation additives were obtained under equilibrium conditions using Attension Theta optical tensiometer. Their adsorption and desorption profiles were measured using Quartz Crystal Microbalancing with Dissipation monitoring (QCM-D). The degree of aggregation of abatacept was assessed based on size exclusion measurement.
  
  
  RESULTS
  Adsorption of abatacept at the oil/water interface was shown. Polysorbat 80 was more effective than Poloxamer 188 in preventing abatacept adsorption. Moreover, it was noted that some of the adsorbed abatacept molecules were not desorbed readily upon buffer rinse. Finally, no homogeneous aggregation was observed at room temperature and a slight increase of aggregation was only observed for samples measured at 40°C which can be prevented using Polysorbate 80.
  
  
  CONCLUSIONS
  Interfacial adsorption of proteins is the key step and maybe responsible for the phenomenon of soluble-protein loss when contacting silicone oil and the irreversible adsorption of protein may be associated with protein denaturation/aggregation.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903, USA. jinjiang.li@bms.com
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Li
authors.forename: Swathi
authors.initials: S
authors.lastname: Pinnamaneni
authors.forename: Yong
authors.initials: Y
authors.lastname: Quan
authors.forename: Archana
authors.initials: A
authors.lastname: Jaiswal
authors.forename: Fredrik I
authors.initials: FI
authors.lastname: Andersson
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000069594:Abatacept; D000327:Adsorption; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D018796:Immunoconjugates / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D020442:Poloxamer / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D012827:Silicone Oils / Q000737:chemistry*; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D018796:Immunoconjugates; D011136:Polysorbates; D012827:Silicone Oils; D013501:Surface-Active Agents; D020442:Poloxamer; D000069594:Abatacept