title: Intermolecular Interactions and the Viscosity of Highly Concentrated Monoclonal Antibody Solutions.
abstract: OBJECTIVE
  The large increase in viscosity of highly concentrated monoclonal antibody solutions can be challenging for downstream processing, drug formulation, and delivery steps. The objective of this work was to examine the viscosity of highly concentrated solutions of a high purity IgG1 monoclonal antibody over a wide range of protein concentrations, solution pH, ionic strength, and in the presence / absence of different excipients.
  
  
  METHODS
  Experiments were performed with an IgG1 monoclonal antibody provided by Amgen. The steady-state viscosity was evaluated using a Rheometrics strain-controlled rotational rheometer with a concentric cylinder geometry.
  
  
  RESULTS
  The viscosity data were well-described by the Mooney equation. The data were analyzed in terms of the antibody virial coefficients obtained from osmotic pressure data evaluated under the same conditions. The viscosity coefficient in the absence of excipients was well correlated with the third osmotic virial coefficient, which has a negative value (corresponding to short range attractive interactions) at the pH and ionic strength examined in this work.
  
  
  CONCLUSIONS
  These results provide important insights into the effects of intermolecular protein-protein interactions on the behavior of highly concentrated antibody solutions.
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Binabaji
authors.forename: Junfen
authors.initials: J
authors.lastname: Ma
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Zydney
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry; D009994:Osmolar Concentration; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal; D005079:Excipients; D007074:Immunoglobulin G; D019999:Pharmaceutical Solutions
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