Effect of Particle Formation Process on Characteristicsand Aerosol Performance of Respirable Protein Powders

Pulmonary delivery of biopharmaceuticalsmay enable targeted local therapeutic effect and noninvasive systemic administration. Dry powder inhaler(DPI) delivery is an established patient-friendly approach for delivering large molecules to the lungs; however, the complexities of balancing protein stability with aerosol performance require that the design space of biopharmaceuticalDPI formulations is rigorously explored. Utilizing four rationally selected formulations obtained using identical atomization conditions, an extensive study of the effect of the particle formation process ( spray dryingor spray freeze-drying) on powder properties, aerosol performance, and protein stability was performed. Multiple linear regression analysis was used to understand the relationship between powder properties, device dispersion mechanism, and aerosol performance. Spray dryingand spray freeze-drying, despite the same spraying conditions, produced powders with vastly different physical characteristics, though similar a...