Spray-Dried Monoclonal Antibody Suspension for High-Concentration and Low-Viscosity Subcutaneous Injection.

Administration of highly concentrated monoclonal antibodies (mAbs) through injection is often not possible as the viscosity can be readily above 50 mPa·s when the concentration exceeds 150 mg/mL. Besides, highly concentrated mAb solutions always exhibit increased aggregation propensity and lower stability, which raise the difficulty for the successful development of highly concentrated mAb formulations. We hereby explored the possibility of suspension as another formulation form for high-concentration proteins to reduce viscosity and maintain stability. Specifically, we demonstrated that spray drying can serve as a process to prepare particles for suspension. Particles prepared from formulations with different mAb/trehalose mass ratios displayed good physical stability and antibody binding affinity, as indicated by circular dichroism, fluorescence spectroscopy, and surface plasmon resonance (SPR)-based bioassay analyses. During spray drying, a surface tension-dominated enrichment of mAb on the particle surface was observed, but this did not show a significant negative impact on mAb stability. Spray-dried particles were subsequently suspended into benzyl benzoate, and the resulting suspension showed good stability and a lower viscosity when compared to its counterpart solution. Furthermore, mAbs recovered from the suspension maintained their conformational structure. Our study demonstrated that the suspension displayed low viscosity and good physical stability, so it may offer novel opportunities for the preparation of highly concentrated protein formulations.