Primary Packaging Hydrophilicity/Hydrophobicity: A Critical Factor Governing Visible-Bubbles during Reconstitution Process of Lyophilized High-Concentration Monoclonal Antibody Formulations

Driven by the evolving demands of modern pharmaceutical industry, high-concentration monoclonal antibody formulations (HCMFs) have emerged as a central research hotspot in biopharmaceutical development, attributable to their merits such as low administration volume and reduced medical expenditure. For lyophilized HCMFs, reconstitution performance serves as a critical quality attribute of equivalent importance to long-term storage stability. As components in direct contact with lyophilized drug products, primary packaging containers are indispensable critical excipients for pharmaceutical preparation. This work systematically investigated the effects of inner surface characteristics of glass vials on the long-term stability and reconstitution behaviors of lyophilized HCMFs. The results demonstrated that the surface hydrophilicity/hydrophobicity of vial walls exerted no remarkable influence on the physicochemical stability of mAb-X during prolonged storage. Nevertheless, in the reconstitution process, the intrinsically high viscosity of concentrated mAb solutions, combined with the ultralow surface free energy, intense hydrophobicity and weakened contact line pinning effect of such vials, triggered massive visible-bubbles to adhere beneath the liquid-solid interface. These trapped bubbles failed to ascend and dissipate along the inner walls and bottom of vials. Collectively, this study verifies that hydrophobic primary packaging materials, when adopted as storage containers for lyophilized HCMFs, will induce severe reconstitution defects, which may further lead to inaccurate dosing and compromised clinical operability.