Evaluation of Effects of Histidine Buffer on the Stability of Infliximab Formulation

OBJECTIVE To identify the optimal buffering agent suitable for infliximab formulations and to further evaluate its physical and freeze-thaw stability.

METHODS The study involved two primary buffering agents(histidine and phosphate), and assessesed the impact of varying pH levels, stabilizers, and surfactants on the aggregation content of infliximab. A detailed analysis was performed to evaluate the physical and freeze-thaw stability of infliximab in formulations containing histidine and phosphate buffers.

RESULTS In liquid formulations, infliximab with histidine as the buffering agent exhibited lower aggregation content and higher stability. Its physical stability parameters, including melting temperature, aggregation onset temperature, and diffusion interaction coefficient were superior to those in the phosphate system; the freeze-drying stability parameter(glass transition temperature of maximally freeze concentrated solution and the glass transition temperature) were not expressed statistically significant difference between the two buffer systems. In lyophilized formulations, the phosphate buffer system exhibited significant pH fluctuations during the freeze-thaw process, whereas the histidine buffer remained stable.

CONCLUSION Histidine is selected as the optimal buffering agent for infliximab formulations and demonstrating superior physical stability.