(464f) Effects of Buffer, pH, and Excipients on the Viscoelastic Properties of the NIST Mab Formulations at the Air-Water Interface Explored Using Passive Microrheology

Development of novel protein-based therapeutics, such as monoclonal antibodies (mAbs), as efficient therapeutics for a wide variety of disease is often limited due to challenges associated with maintaining the stability of these formulations during manufacturing, storage, and clinical administration. An undesirable consequence of instability of protein therapeutics is formation of protein particles that can cause unwanted immune responses and may also result in a lowering of the drug efficacy. mAbs can adsorb to interfaces and have the potential to undergo partial unfolding as well as form viscoelastic gels. Further, the viscoelastic properties may be corelated with their aggregation potential. In this work, an interfacial microrheology technique was used to corelate the surface adsorption and evolution of surface rheology of the National Institute of Standards and Technology (NIST) mAb reference material (NIST mAb) adsorbing to the air-water interface. The evolution of surface adsorption, and the viscoelastic properties of the NIST mAb was recorded in four formulation conditions: two different buffers (histidine vs. phosphate buffered saline) and two different pHs (6.0 and 7.6). Our results show that for all protein formulations, initially the films demonstrate a purely viscous nature at the interface. However, with time, the protein films undergo a transition to more viscoelastic gels. When this transition occurs depends on the buffer formulations. Specifically, NIST mAb in histidine buffer at pH 6.0 shows a pure viscous character for the longest time, while NIST mAb formulated in PBS at 7.4 shows the quickest transition to a more viscoelastic gel.

Addition of polysorbate, a FDA approved surfactant added as excipient to prevent protein particle formation, shows a purely viscous nature at the interface, suggesting that formation of viscoelastic gels are necessary for protein particle formation at the interface.