title: Sustained mechanical and clinical functionality of the flexhaler dry powder inhaler.
abstract: Flexhaler is a multiple-dose, inspiratory flow-driven dry powder inhaler that is a newer version of Turbuhaler, and is identical to the Symbicort Turbuhaler. Sustained performance is of the utmost importance to ensure consistent drug delivery throughout the lifespan of the inhaler. We report functionality testing results of Flexhaler inhalers used in two large-scale 12-week studies of budesonide (Pulmicort) and returned for testing. Functionality tests included measurement of airflow resistance and inspection of vital parts for the mechanical functionality of the inhaler, including visual inspection of the indicator wheel and function check of dose loading. In addition, delivered dose, particle size distribution, moisture content, and microbial counts were evaluated. Seven hundred sixteen out of 720 units were returned. Airflow resistance was not affected by the handling of the Flexhaler inhalers during use (prior to use, average airflow resistance: 67 Pa(0.5)*s*L(-1); returned inhalers: 66 and 67 Pa(0.5)*s*L(-1) in each study, respectively. The average dose delivered remained as intended after prolonged clinical use [95% (range 88 -103%) vs. reference of 99% (range 93-104%) before issue]. Relative fine particle dose ( <5 mum) after use was 107% (range 96-111%) of the reference value before issue. Moisture content in the inhaler desiccant was 3-25%, suggesting variability in storage conditions. Among the 28 inhalers randomly selected for microbiological testing there was no or very limited microbial growth. All 14 inhalers returned with functionality issues operated as intended and no reported functionality issues could be confirmed. Flexhaler inhalers operated as intended during these two clinical trials. These results should reassure both clinicians and patients with respect to the consistent quality of this unit for the delivery of dry powder formulations for inhalation.
authors.affiliation: Pharmaceutical and Analytical R&D, AstraZeneca R&D Lund, Lund SE-221 87 Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lööf
authors.forename: Peter
authors.initials: P
authors.lastname: Elfman
authors.forename: Pelle
authors.initials: P
authors.lastname: Ström
authors.forename: Anders
authors.initials: A
authors.lastname: Törngren
authors.forename: Lars
authors.initials: L
authors.lastname: Borgström
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D015169:Colony Count, Microbial; D004355:Drug Stability; D004356:Drug Storage; D004867:Equipment Design; D005260:Female; D006801:Humans; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D009330:Nebulizers and Vaporizers / Q000592:standards*; D010316:Particle Size; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide