Stabilizing effect of HP-β-CD on infliximab in liquid formulations and a solid formulation produced by electrospinning

Abstract

The development of stable biopharmaceutical formulations, such as monoclonal antibodies, poses a great challenge in the pharmaceutical industry. This study investigated the stabilizing effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in liquid and solid formulations of infliximab during processing and storage. The solid formulation was produced by a scaled-up high-speed electrospinning method, resulting in a product suitable for reconstitution with excellent dissolution properties. Liquid formulations contained exclusively HP-β-CD as a stabilizing excipient at different concentrations. Both types of formulations were stored under various conditions for up to 6 months, and infliximab stability was compared based on monomer recovery and the analysis of fragments and aggregates. The solid formulation stored at low (-18 °C, 4 °C) temperatures and lower humidity conditions show the most promising results. Moreover, the monomer loss was less than 10 % even at room temperature storage after 2 months, indicating a potentially good temperature tolerance. Increasing HP-β-CD content in liquid formulations significantly improved the long-term stability of infliximab while enhancing protection against mechanical stress. Furthermore, to better understand the stabilizing mechanism of HP-β-CD on infliximab, the molecular interactions were investigated by bio-layer interferometry and isothermal titration calorimetry methods. The experiments proved that the presence of HP-β-CD decreased infliximab self-interaction, correlating with the aggregation-suppressing effect of HP-β-CD observed during the stress- and long-term stability studies. The results demonstrate the potential of HP-β-CD as a stabilizing excipient in liquid and solid formulations of infliximab.