Stabilisation of a monoclonal antibody formulation in the presence of poloxamer 188 and related PEG/PPG systems

Abstract

Surfactants like poloxamer 188 are commonly used to stabilise antibody and other protein drug products. This study investigated the impact of poloxamer 188 on the stability of an antibody model protein in an aqueous buffered solution in comparison to mixtures composed of both polyethylene glycol and polypropylene glycol block polymers. The separate consideration of the block polymer units is important to understand the stabilising characteristics of poloxamer 188 and its degradation products. Therefore, interfacial stress was applied using a 48-hour shaking test to evaluate the stabilisation properties of the surfactants for an antibody. The effect of shaking was investigated by visual inspection, nephelometric turbidity measurement, size exclusion chromatography, and sub-visible particle formationvia backgrounded membrane imaging. Surface tension measurements revealed the impact of polyethylene glycol and polypropylene glycol on the air-water interface and showed that high surface activity is not the only decisive factor for protein stabilisation. It was determined that all excipients have the capacity to protect the antibody from protein particle formation to a certain extent. Polypropylene glycol performed better than polyethylene glycol due to a higher tendency to interact with the air-water interface. Surprisingly, mixtures of polyethylene glycol and polypropylene glycol, similar to their molecular weight ratio in poloxamer 188, led to comparable stabilisation properties to those of the triblock polymer poloxamer. This study indicates different stabilisation mechanisms for polyethylene glycol and polypropylene glycol combined in the poloxamer 188 molecule.