title: Multi-breath dry powder inhaler for delivery of cohesive powders in the treatment of bronchiectasis.
abstract: A series of co-engineered macrolide-mannitol particles were successfully prepared using azithromycin (AZ) as a model drug. The formulation was designed to target local inflammation and bacterial colonization, via the macrolide component, while the mannitol acted as mucolytic and taste-masking agent. The engineered particles were evaluated in terms of their physico-chemical properties and aerosol performance when delivered via a novel high-payload dry powder Orbital(™) inhaler device that operates via multiple inhalation manoeuvres. All formulations prepared were of suitable size for inhalation drug delivery and contained a mixture of amorphous AZ with crystalline mannitol. A co-spray dried formulation containing 200 mg of 50:50 w/w AZ: mannitol had 57.6% ± 7.6% delivery efficiency with a fine particle fraction (≤6.8 µm) of the emitted aerosol cloud being 80.4% ± 1.1%, with minimal throat deposition (5.3 ± 0.9%). Subsequently, it can be concluded that the use of this device in combination with the co-engineered macrolide-mannitol therapy may provide a means of treating bronchiectasis.
authors.affiliation: Department of Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney , NSW , Australia .
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.forename: Rania O
authors.initials: RO
authors.lastname: Salama
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Crapper
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D017963:Azithromycin / Q000008:administration & dosage* / Q000737:chemistry; D001987:Bronchiectasis / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry*; D010316:Particle Size; D011208:Powders
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D005079:Excipients; D011208:Powders; D008353:Mannitol; D017963:Azithromycin
keywords: Bronchiectasis; dry powder inhaler; inhalation; macrolides; mucolytics; orbital