Improvement of Aerodynamic Behavior of Spray-Freeze Dried IgG Powder Applying Amino Acids

Introduction: Improved stabilization efficiency of processedpowders has been observed via spray freeze drying (SFD) of antibody dried-formulations. The competence of different amino acids was compared with special focus on aerodynamic properties.

Methods: Trehalose in 1:1 of mass ratio to IgG besides Leucine, Phenyl alanine and Glycine in 1:4 and 1:8 of mass ratio to IgG were prepared through SFD. Size-exclusion chromatography (SEC-HPLC) employed to determine the soluble aggregates. Twin stage impinger (TSI), laser light scattering and scanning electron microscopy (SEM) utilized to characterize particle properties. Powder density and thermal behavior analyzed through graduated glass cylinder and differential scanning calorimetry (DSC).

Results: Powders were well-stabilized (soluble aggregates: 0.19- 2.68 %). The least particle size achieved using Phenylalanine at lower ratio (8.47 μm). The largest particles and the lowest powder recovery observed in Glycine-containing powders. Excluding Phenylalanine at mass ratio 1:8, all powders were desirably porous with low densities. Best aerosolization behavior was resulted from Leucine and Phenylalanine at 1:4 of mass ratio to IgG, with FPF values of 65.90 and 59.20% respectively.

Conclusion: SFD would be a favorable method to process IgG powder. Hydrophobic amino acids not only stabilized antibody against aggregation, but prominently improved aerosolization efficiency of powders.