Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations

• DOI: 10.1021/acs.molpharmaceut.3c00991
• Publication Date: 2024-03-02T14:26:00Z
• Authors: Han Gao; Xin-Zhe Ge; Jia-Wei Liu; Si-Tao Wang; Jie Xu; Wei-Jie Fang
• Keywords: Omalizumab

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period time in reconstitution process, which greatly reduces use efficiency. It is necessary to understand forming breaking mechanism VBs key factor efficient safe administration biopharmaceutical injection. The effects different thermal treatments on volume stability omalizumab, mAb-1, mAb-2 were investigated. internal microvoids cake characterized by scanning electron microscopy mercury intrusion porosimetry. Electron paramagnetic resonance was applied obtain molecular mobility protein during annealing. A large number process unannealed remained time. When annealing steps added, dramatically reduced. annealed at an aggressive temperature (i.e., −6 °C), although decreased, aggregation acidic species increased significantly. Thus, our observations highlight importance setting additional step with suitable temperature, contributes reducing while maintaining high concentration formulation.