title: Can 'extrafine' dry powder aerosols improve lung deposition?
abstract: There is increasing interest in the use of so-called 'extrafine' aerosols to target the small airways in the management of asthma and COPD. Using previously presented deposition data, we assessed whether submicron (<1μm) particles can improve central and deep lung deposition. Our data show instead that particles in the range 1-3μm are much more relevant in this respect. Based on this finding the Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster (Fostair) NEXThaler ICS/LABA combination DPIs were tested in vitro as a function of the pressure drop (2, 4 and 6kPa) across the inhaler. Obtained fine particle fractions (FPFs) <5μm (as percent of label claim) were divided into subfractions <1, 1-3 and 3-5μm. Differences of up to a factor of 4 were found between the best (Turbuhaler) and worst performing DPI (Elpenhaler), particularly for the FPF in the size range 1-3μm. The NEXThaler, described as delivering 'extrafine' particles, did not appear to be superior in this size range. The marked differences in amount and size distribution of the aerosols between the devices in this study must cause significant differences in the total lung dose and drug distribution over the airways.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands. Electronic address: a.h.de.boer@rug.nl.
authors.forename: Anne H
authors.initials: AH
authors.lastname: de Boer
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
authors.forename: Doetie
authors.initials: D
authors.lastname: Gjaltema
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D058995:Dry Powder Inhalers; D006801:Humans; D008168:Lung / Q000378:metabolism*; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D000420:Albuterol
keywords: Dry powder inhaler; Extrafine aerosol; ICS; Lung deposition; Small airway targeting; Submicron particles