Monday, May 19, 2008 - 10:40 AM
Medical Arts Building, Rm M-136 (Queensborough Community College)
175

Ultrasonic Storage Modulus as a Novel Parameter for Analyzing Protein-Protein Interactions in High Protein Concentration Solutions

Devendra Kalonia, University of Connecticut, Storrs, CT

Abstract: Current market trends for high dose therapeutic proteins require concentrated liquid formulations for the patient convenience, in home subcutaneous administration, to cut manufacturing costs and to improve product marketability. Protein-protein interactions in these solutions need to be characterized to prepare these solutions with desired viscosity and stability during storage. An ultrasonic shear rheometer based on impedance analysis of piezoelectric quartz crystals was developed for rheological analysis and viscosity measurement of liquids at small sample volumes. Rheological analysis and biophysical characterization conducted on a model monoclonal antibody, IgG2, between pH 4.0 to 9.0 and ionic strengths between 4 mM and 300 mM demonstrated the significant role of protein-protein interactions in governing the solution behavior of protein in concentrated solutions. Results indicated that solution G′ could serve as a parameter for assessing protein-protein interactions in high protein concentration solutions. Its validity for this purpose was confirmed by static and dynamic light scattering measurements under relatively dilute solutions. The measured second virial coefficient (B22) and interaction parameter (kd) were found to be consistent with the solution G′ measurements.