A technical feasibility study of dornase alfa delivery with eFlow® vibrating membrane nebulizers: aerosol characteristics and physicochemical stability.
Dornase alfa (Pulmozyme®) is an inhaled mucus-active drug that decreases viscoelasticity of sputum in vitro, improves lung function and reduces respiratory exacerbations in cystic fibrosis (CF) patients of 5 years age and older. The regulatory approval of dornase alfa 15 years ago stipulated that only certain jet nebulizer-compressor combinations should be used to deliver the drug. Since that time there have been significant advances in aerosol delivery technology, including development of electronic perforated vibrating membrane devices. Three independent laboratories studied aerosol characteristics, nebulization time, dose delivery, and stability of dornase alfa after nebulization to determine the feasibility of using perforated vibrating membrane devices to deliver the drug. These studies determined that the eFlow® vibrating membrane technology delivers dornase alfa more rapidly and efficiently than jet nebulizers, and does not affect the physicochemical properties of the drug. These in vitro results demonstrate only the technical feasibility of using vibrating membrane devices to deliver dornase alfa. Clinical studies will be required before any conclusions can be made regarding clinical safety and efficacy of these drug-device combinations for cystic fibrosis.
Late Stage Pharmaceutical and Processing Development, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Thomas
T
Scherer
David E
DE
Geller
Laura
L
Owyang
Marcus
M
Tservistas
Manfred
M
Keller
Norbert
N
Boden
Kenneth C
KC
Kesser
Steven J
SJ
Shire
D000336:Aerosols; D055598:Chemical Phenomena; D003550:Cystic Fibrosis / Q000188:drug therapy; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry*; D016503:Drug Delivery Systems; D004795:Enzyme Stability; D057487:Enzyme Therapy / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D007700:Kinetics; D008567:Membranes, Artificial; D036501:Metered Dose Inhalers; D010316:Particle Size; D011786:Quality Control; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D013678:Technology, Pharmaceutical; D014732:Vibration
D000336:Aerosols; D008567:Membranes, Artificial; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I