Development of microparticulate powders of a therapeutic protein for pulmonary delivery

Recombinant human deoxyribonuclease I (rhDNase I) is a therapeutic protein used to manage the symptoms of cystic fibrosis (CF). Currently, it is available only as a solution for nebulisation that requires refrigeration and a stationary time-consuming administration process. The development of rhDNase I as an inhaled dry powder for administration with a dry powder inhaler (DPI) would (i) reduce the treatment burden for CF patients, (ii) enable transportation and storage at ambient conditions and (iii) allow for rapid administration on the go. In this study, bovine DNase I was used as a model protein. Spray drying, which is a single-step continuous manufacturing process, was used to produce dry powders of bovine DNase I and fine-tune particle properties for pulmonary delivery. A 23 factorial design of experiments (DoE) was undertaken, and process parameters adjusted were: solution flow rate, atomising air flow rate, and outlet temperature. The resulting powders were characterised in terms of particle size distribution, process yield, protein recovery yield, and particle shape. ANOVA analysis was used to identify and optimize important process parameters and investigate correlations with particle characteristics. The morphology and aerodynamic performance of selected powders were determined by scanning electron microscopy (SEM), focused ion beam – SEM, and cascade impaction using a next generation impactor (NGI). The moisture sorption behaviour and crystallinity of selected powders were obtained by dynamic vapor sorption (DVS) and powder X-ray diffraction (PXRD), respectively. Key findings and the direction of future work will be outlined in the poster.