Stabilization of spray-dried monoclonal antibody formulations with polymeric excipients.

Spray drying is an emerging continuous manufacturing approach with significant potential for producing stable solid formulations of biologic drug products such as peptides, proteins and oligonucleotides. However, these sensitive molecules on exposure to thermal, shear, and interfacial stresses during spray drying may experience structural perturbations that compromise long-term stability. This study evaluated several polymeric excipients as stabilizers in spray-dried monoclonal antibody formulations and compared their performance with conventional sugar excipients, trehalose and mannitol. Formulations were prepared at a 1:1 (w/w) protein-to-excipient ratio and spray dried, and the resulting powders were subjected to accelerated storage at 40 °C. Particle size distribution, morphology, and residual moisture content were characterized. Protein physical stability and secondary structure were evaluated using size exclusion chromatography and solid-state Fourier transform infrared spectroscopy, respectively. Solid-state nuclear magnetic resonance spectroscopy and X-ray photoelectron spectroscopy were used to study protein-excipient phase miscibility and particle surface composition, respectively, in the spray-dried solids. Hydrolyzed gelatin provided the most robust stabilization of the mAb, resulting in a fivefold reduction in monomer loss compared to trehalose after 90 days storage at 40 °C. (2-Hydroxypropyl)-β-cyclodextrin showed stabilization comparable to trehalose while reducing the mAb surface exposure. High molecular weight polyvinylpyrrolidone (PVP K90) showed better mAb stabilization compared to its low molecular weight grade (PVP K30). Whereas dextran, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose were less effective in their ability to stabilize the mAb. These findings highlight the critical role of excipient selection in improving the stability of spray-dried monoclonal antibody formulations.