title: The Cyclops for pulmonary delivery of aminoglycosides; a new member of the Twincer™ family.
abstract: Patients infected with pathogenic bacteria have to be treated with antibiotics. When the infection is in the lungs, as for instance in cystic fibrosis, bronchiectasis and tuberculosis, inhaled antibiotics have certain advantages over systemically administered antibiotics. In this study, it is shown that re-designing the Twincer™ high dose disposable inhaler into a device named Cyclops enables effective dispersion of up to 50mg of pure spray dried tobramycin. This proves that spray dried tobramycin powders in the preferred size range for inhalation can be administered without applying complex particle engineering techniques and/or using excipients. Only some coarse sweeper crystals added separately are desired to minimise the inhaler losses to less than 20% at 4 kPa. The fine particle fractions <5 μm of the aerosol obtained from the Cyclops closely resemble the primary particle size distribution of the spray dried tobramycin powder. Moreover, without any further optimisation the Cyclops performs good with other spray dried aminoglycosides such as kanamycin and amikacin too. Therefore, the results of this study show that with an appropriate inhaler design, adapted to the physico-chemical properties of a particular drug or drug class, excellent dispersion can be achieved for high doses of pure (spray dried) drug.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: m.hoppentocht@rug.nl.
authors.forename: M
authors.initials: M
authors.lastname: Hoppentocht
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Groningen, The Netherlands.
authors.forename: O W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: de Boer
mesh_terms: D000280:Administration, Inhalation; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D058995:Dry Powder Inhalers / Q000379:methods; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D008911:Minocycline / Q000008:administration & dosage* / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014031:Tobramycin / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000617:Aminoglycosides; D005079:Excipients; D011208:Powders; D008911:Minocycline; D014031:Tobramycin
keywords: Aminoglycosides; Antibiotics; Cystic fibrosis; Disposable inhaler; Dry powder dispersion; High drug dose; Tuberculosis