Electrostatic spray drying for monoclonal antibody formulation.

ABSTRACT

This study explored the feasibility of electrostatic spray drying for producing a monoclonal antibody (mAb) powder formulation at lower drying temperatures than conventional spray drying and its effect on protein stability. A mAb formulation was dried by either conventional spray drying or electrostatic spray drying with charge (ESD). The protein powders were then characterized using solid-state Fourier transform infrared spectroscopy (ssFTIR), differential scanning calorimetry (DSC), size exclusion chromatography (SEC), and solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS). Particle characterizations such as BET surface area, particle size distribution, and particle morphology were also performed. Conventional spray drying of the mAb formulation at the inlet temperature of 70 °C failed to generate dry powders due to poor drying efficiency; electrostatic spray drying at the same temperature and 5 kV charge enabled the formation of powder formulation with satisfactory moisture contents. Deconvoluted peak areas of deuterated samples from the ssHDX-MS study showed a good correlation with the loss of the monomeric peak area measured by size exclusion chromatography in the 90-day accelerated stability study conducted at 40 °C. Low-temperature (70 °C inlet temperature) drying with an electrostatic charge (5 kV) led to better protein physical stability as compared with the samples spray-dried at the high temperature (130 °C inlet temperature) without charge. This study shows that electrostatic spray drying can produce solid monoclonal antibody formulation at lower inlet temperature than traditional spray drying with better physical stability.