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 theviscosity can be readily above 50 mPamiddots when the concentration exceeds 150 mg/mL. Besides, highly concentrated mAb solutionsalways exhibit increased aggregation propensity and lower stability, which raise the difficulty for the successful development of highlyconcentrated 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 aprocess to prepare particles for suspension. Particles prepared from formulations with different mAb/trehalose mass ratios displayedgood physical stability and antibody binding affinity, as indicated by circular dichroism,fluorescence spectroscopy, and surfaceplasmon resonance (SPR)-based bioassay analyses. During spray drying, a surface tension-dominated enrichment of mAb on theparticle surface was observed, but this did not show a significant negative impact on mAb stability. Spray-dried particles weresubsequently suspended into benzyl benzoate, and the resulting suspension showed good stability and a lower viscosity whencompared 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 opportunitiesfor the preparation of highly concentrated protein formulations.

Automated summary

This study explored the use of suspension as a formulation form for highly concentrated proteins to reduce viscosity and maintain stability. Spray drying was demonstrated as an effective process to prepare particles for suspension, which showed good physical stability and antibody binding affinity. mAbs recovered from the suspension maintained their conformational structure.