Linking aggregation and interfacial properties in monoclonal antibody-surfactant formulations

Area of Science:

• Protein aggregation
• Formulation development
• Biopharmaceutical science

Background:

• Monoclonal antibodies (mAbs) are crucial therapeutics, but their aggregation at air-solution interfaces poses formulation challenges.
• Interfacial stresses during adsorption contribute significantly to mAb aggregation.
• Controlling mAb aggregation is vital for therapeutic efficacy and stability.

Purpose of the Study:

• To investigate the impact of common pharmaceutical surfactants on mAb aggregation and interfacial behavior.
• To elucidate the mechanisms by which surfactants mitigate interfacial aggregation of mAbs.
• To correlate mAb aggregation with interfacial properties influenced by surfactant type and concentration.

Main Methods:

• Agitation-induced aggregation was assessed using size-exclusion chromatography, flow cytometry, and light obscuration.
• Interfacial behavior was studied by analyzing fluid film drainage between mAb-surfactant interfaces.
• Surface tension, interfacial rheology, and surface tension gradients were measured.

Main Results:

• Surfactants (polysorbate-20, poloxamer-188, polyethylene glycol) significantly reduced mAb aggregate formation.
• Soluble aggregate formation correlated with mAb surface concentration, while insoluble aggregates depended on adsorbed mAb network formation.
• Fluid film drainage revealed surfactant-dependent mechanisms including interfacial rheology and surface tension gradients, impacting mAb aggregation.

Conclusions:

• Pharmaceutical surfactants are effective in preventing mAb aggregation by modifying interfacial behavior.
• The type and concentration of surfactant critically influence the aggregation pathway and stability of mAb formulations.
• This research provides insights for optimizing biopharmaceutical formulations to enhance therapeutic protein stability and efficacy.