title: The development of a single-use, capsule-free multi-breath tobramycin dry powder inhaler for the treatment of cystic fibrosis.
abstract: The aerosol performance and delivery characteristics of tobramycin for the treatment of respiratory infection were evaluated using the Orbital™, a multi-breath, high dose, dry powder inhaler (DPI). Micronised tobramycin was prepared and tested in the Orbital and in the commercially available TOBI Podhaler (Novartis AG). Furthermore, the TOBI Podhaler formulation containing tobramycin as Pulmospheres was tested in both the commercial Podhaler device (T-326) and Orbital for comparison. By varying the puck geometry of the Orbital, it was possible to deliver equivalent doses of micronised tobramycin (114.09±5.86mg) to that of the Podhaler Pulmosphere product (116.01±2.59mg) over 4 sequential simulated breaths (60Lmin-1for 4s) without the need for multiple capsules. In general, the aerosol performance of the micronised tobramycin from the Orbital was higher than the T-326 Podhaler device, with fine particle fraction (FPF) of 44.99%±1.09% and 37.03%±0.86%, respectively. When testing the Pulmosphere powder in the two devices, the T-326 had marginally better performance with a FPF of 68.77%±2.10% compared to 61.30%±3.45%. This is to be expected since the TOBI Podhaler and Pulmosphere are an optimised powder and device combination. The Orbital was shown to be capable of delivering high efficiency, high dose antibiotic therapy for inhalation without the need for the use of multiple capsules as used in current devices. This approach may pave the way for a number of antibiotic therapies and medicaments where high dose respiratory deposition is required.
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Padroni
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Pharmaxis Pty. Ltd., 20 Rodborough Rd., Frenchs Forest, Sydney, NSW 2086, Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.affiliation: Pharmaxis Pty. Ltd., 20 Rodborough Rd., Frenchs Forest, Sydney, NSW 2086, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Crapper
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia. Electronic address: paul.young@sydney.edu.au.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D055598:Chemical Phenomena; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004339:Drug Compounding; D058995:Dry Powder Inhalers / Q000295:instrumentation*; D010316:Particle Size; D011208:Powders; D014031:Tobramycin / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000336:Aerosols; D011208:Powders; D014031:Tobramycin
keywords: Crystalline; High dose dry powder inhaler; Orbital; Tobramycin