Dynamic Properties of Novel Excipient Suggest Mechanism for Improved Performance in Liquid Stabilization of Protein Biologics

摘要

To improve liquid formulation stability, formulators employ various excipients designed to stabilize protein drugs, including buffers, salts, sugars, and surfactants. One of the roles of surfactants is to protect the protein drug from surface interactions that can destabilize the protein. Protein drug products formulated with surfactants usually contain either a polysorbate or poloxamer. Even in the presence of these surfactants, protein drug stability is often insufficient, particularly because of agitation-induced aggregation. FM1000 is one of a series of surfactants containing an alkyl chain, an amino acid, and a polyetheramine. The characterization of the dynamics of FM1000 at various water/hydrophobic interfaces was compared to Polysorbate 20, Polysorbate 80, and Poloxamer 188. FM1000 stabilizes an interface 1-2 orders of magnitude faster than all three of these surfactants, even in the presence of protein. The faster dynamics leads to improved stabilization of model protein biologic drugs IgG and abatacept against agitation-induced aggregation. These results provide mechanistic understanding of the key causes and drivers of protein aggregation.