Development of Inhalable Azithromycin/Protein Dry Powder Dry Powders for Treating Cystic Fibrosis

Abstract

The aim of this study is to develop an inhalable dry powder formulation containing azithromycin (AZ) and a model protein representative of recombinant human DNase (rhDNase) for potential use in the treatment of cystic fibrosis (CF). The goal is to produce particles within the respirable aerodynamic range (1-5 µm) to enable effective deposition in the lower airways. A three-fluid nozzle spray drying technique was employed to prepare formulations comprising AZ as the active pharmaceutical ingredient and ovalbumin (OVA) as the model protein. Multiple formulations were evaluated to assess the impact of spray gas flow and concentration on yield, particle size, and protein stability. A design of experiments (DoE) approach was applied to optimize the spray drying process. The results demonstrated that spray gas flow had a significant influence on both particle size and yield, with optimal settings producing particles in the desired aerodynamic range. Scanning electron microscopy (SEM) was used to evaluate particle morphology and geometric size, verifying consistency across formulations. In parallel, aerodynamic particle sizing confirmed that a high fine particle fraction (FPF) was achieved, indicating suitability for pulmonary delivery. ELISA analysis demonstrated that OVA retained its structure and function following spray drying. In conclusion, an optimized dry powder formulation comprising AZ and OVA was successfully developed, exhibiting favorable aerodynamic properties, high yield, and preserved protein integrity. These findings support the feasibility of co-spray drying AZ with a protein component, laying the groundwork for future development involving rhDNase for dual-drug inhalation therapy in CF.