Paper Number
BM12 

Session
Biological Macromolecules: Proteins, Cellulosic Biomass and other Biomaterials

Title
Dilatation air bubbles in solution: A rheological study of their effects on therapeutic antibody stability

Presentation Date and Time
October 12, 2015 (Monday) 4:25

Track / Room
Track 4 / Constellation F

Authors (Click on name to view author profile)

1. Lin, Gigi L. (Stanford University)
2. Pathak, Jai (Medimmune, Formulation Sciences Department)
3. Riguero, Valeria (MedImmune, Inc., Protein Purification Sciences Dept.)
4. Carlson, Marcia (MedImmune, Inc.)
5. Buff, Jean (ETH Zurich, Food Process Engineering)
6. Fuller, Gerald G. (Stanford University, Department of Chemical Engineering)

Author and Affiliation Lines (in printed abstract book)
Gigi L. Lin¹, Jai Pathak², Valeria Riguero³, Marcia Carlson³, Jean Buff⁴, and Gerald G. Fuller^1
1Department of Chemical Engineering, Stanford University, Stanford, CA; ²Formulation Sciences Department, Medimmune, Gaithersburg, MD 20878; ³MedImmune, Inc., Gaithersburg, CA; ⁴Food Process Engineering, ETH Zurich, Zurich, Switzerland

Speaker / Presenter 
Lin, Gigi L.

Text of Abstract
Monoclonal antibody drugs are a growing class of biologic therapeutics with high specificity in the treatment of cancer and various other indications. Although interfacial hydrodynamic stresses that are distinct from bulk shear are routinely encountered by monoclonal antibodies under typical manufacturing, filling and shipping conditions, the physics underlying molecular instability in the form of aggregate and particle formation is poorly understood and lumped under the moniker “shear.” Our rheological studies examine well-characterized interfacial modes of fluid kinematics: equal-area shear and dilatation. We find visual evidence that dilatational deformation of the air-solution (A/S) interface is more detrimental to antibody stability when compared to constant-area shear at the interface. This was accomplished with the construction of a dilatational device that uses simultaneous pressure and shape measurements to study the protein’s mechanical stability under interfacial aging. This approach has advantages over traditionally used methods that invoke the Young-Laplace equation, as they inaccurately describe viscoelastic interfaces formed by proteins adsorbed at solution/water interfaces. It offers multiple possibilities for rheological experiments, including step-strain and exponential strain studies. Results indicate that aging time, concentration, and magnitude of dilatational strain influence the onset of yielding of the protein-adsorbed solution/water interface, which can be used to characterize the extent of protein destabilization at the interface.