caa a22 4500 477127533 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012035113276 doi (NATIONALLICENCE)springer-10.1023/A:1012035113276 Spray Dried Powders and Powder Blends of Recombinant Human Deoxyribonuclease (rhDNase) for Aerosol Delivery [Elektronische Daten] [Hak-Kim Chan, Andy Clark, Igor Gonda, Marco Mumenthaler, Chung Hsu] Purpose. We have used rhDNase to investigate the feasibility of developing a dry protein powder aerosol for inhalation delivery. Methods. Powders of rhDNase alone and with sodium chloride were prepared by spray drying. Powder blends were obtained by mixing (tumbling and sieving) pure rhDNase powder with 'carrier' materials (lactose, mannitol or sodium chloride). The weight percent of drug in the blends was between 5 and 70%. The particle size distributions and crystallinity of the spray dried powders were obtained by laser diffraction and X-ray powder diffraction, respectively. Particle morphology was examined by scanning electron microscopy. The ability of the powders and powder blends to be dispersed into respirable aerosols was measured using a Rotahaler™ connected to a multistage liquid impinger operating at 60 L/min. Results. Pure rhDNase powder was quite cohesive with a fine particle fraction (FPF or 'respirable fraction': % wt. of particles < 7 μm in the aerosol cloud) of about 20%. When particles also contained NaCl, the powders were dispersed better to form aerosols. A linear relationship was observed between the NaCl content and FPF for a similar primary size (~3 μm volume median diameter) of particles. The particle morphology of these powders varied systematically with the salt content. For the blends, SEM revealed a monolayer-like adhesion of the fine drug particles to the carriers at drug contents ≥50 % wt. An overall 2-fold increase in FPF of rhDNase in the aerosol cloud was obtained for all the blends compared to the pure drug aerosols. Conclusions. The aerosol properties of spray dried rhDNase powders can be controlled by incorporation of a suitable excipient, such as NaCl, and its relative proportion. Coarse carriers can also enhance the performance of rhDNase dry powder aerosols. Plenum Publishing Corporation, 1997 rhDNase nationallicence dornase alpha nationallicence powder aerosol nationallicence spray drying nationallicence inhalation nationallicence powder blends nationallicence Chan Hak-Kim Department of Pharmacy, University of Sydney, 2006, NSW, Australia aut Clark Andy Inhale Therapeutics, Palo Alto, California aut Gonda Igor Aradigm Corporation, Hayward, California aut Mumenthaler Marco F. Hoffmann—La Roche Ltd, Basel, Switzerland aut Hsu Chung Genentech, Inc., South San Francisco, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 431-437 0724-8741 14:4<431 1997 14 11095 https://doi.org/10.1023/A:1012035113276 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012035113276 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chan Hak-Kim Department of Pharmacy, University of Sydney, 2006, NSW, Australia aut NATIONALLICENCE 700 1- Clark Andy Inhale Therapeutics, Palo Alto, California aut NATIONALLICENCE 700 1- Gonda Igor Aradigm Corporation, Hayward, California aut NATIONALLICENCE 700 1- Mumenthaler Marco F. Hoffmann—La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Hsu Chung Genentech, Inc., South San Francisco, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 431-437 0724-8741 14:4<431 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer