title: Adenosine dry powder inhalation for bronchial challenge testing, part 1: inhaler and formulation development and in vitro performance testing.
abstract: Dry powder administration of adenosine by use of an effective inhaler may be an interesting alternative to nebulisation of adenosine 5'-monophosphate in bronchial challenge testing, because of a shorter administration time and more consistent delivered fine particle dose over the entire dose range. In this study, we tested various powder formulations and classifier based dispersion principles and investigated the in vitro performance of the most promising formulation/classifier combination in a new test inhaler system. Spray-dried formulations of either pure adenosine (100%) or adenosine and lactose as diluent (1% and 10% adenosine) were prepared to cover the entire expected dose range for adenosine (0.01-20mg). All three powders, in all 12 suggested doses, dispersed well with the newly developed test inhaler with a multiple air jet classifier disperser, into aerosols with an average volume median diameter of 3.1μm (3.0-3.3μm). For eleven out of 12 dose steps, the fine particle fractions<5μm as percent of the loaded dose varied within the range of 67-80% (mean: 74%). The new test concept allows for more consistent aerosol delivery over the entire dose range with narrower size distributions than nebulisation and thus may improve adenosine administration in bronchial challenge testing.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: a.j.lexmond@rug.nl.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Lexmond
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: p.hagedoorn@rug.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Pulmonary Medicine and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: e.van.der.wiel@umcg.nl.
authors.forename: Erica
authors.initials: E
authors.lastname: van der Wiel
authors.affiliation: Department of Pulmonary Medicine and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: n.h.t.ten.hacken@umcg.nl.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: h.w.frijlink@rug.nl.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: a.h.de.boer@rug.nl.
authors.forename: Anne H
authors.initials: AH
authors.lastname: de Boer
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000336:Aerosols; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests / Q000295:instrumentation* / Q000379:methods*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D058995:Dry Powder Inhalers; D004867:Equipment Design; D008962:Models, Theoretical; D010316:Particle Size; D010865:Pilot Projects; D013499:Surface Properties
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D000241:Adenosine
keywords: Adenosine; Adenosine 5′-monophosphate; Air classifier technology; Bronchial challenge test; Dry powder inhaler