Adenosine dry powder inhalation for bronchial challenge testing,part 1: Inhaler and formulation development and in vitro performance testing |
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| Institution: | 1. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands;2. Department of Pulmonary Medicine and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;3. Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;1. The University of Sydney, Brain and Mind Centre, The Lambert Initiative for Cannabinoid Therapeutics, Sydney, NSW, Australia;2. The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia;3. The University of Sydney, Faculty of Science, School of Psychology, NSW, Australia;1. Department of Chemistry, St. John’s University, 8000 Utopia Parkway, Queens, NY, USA;2. Department of Chemistry, The City College, City University of New York (CUNY), NY, USA;3. Instituto de Estructura de la Materia, Consejo Superior de Investigaciones científicas, Madrid, Spain;4. The Université du Québec à Trois-Rivières, Department of Chemistry, Biochemistry and Physics, Trois-Rivières, Canada;1. Department of Pharmaceutical Chemistry & Quality Assurance, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai 400 056, India;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bangalore 560 064, India |
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| 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 (0.01–20 mg). 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 3.1 μm (3.0–3.3 μm). For eleven out of 12 dose steps, the fine particle fractions < 5 μm 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. |
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| Keywords: | Bronchial challenge test Adenosine Adenosine 5′-monophosphate Dry powder inhaler Air classifier technology |
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