title: Effect of inhalation profile and throat geometry on predicted lung deposition of budesonide and formoterol (BF) in COPD: An in-vitro comparison of Spiromax with Turbuhaler.
abstract: Successful delivery of inhalation medication to the lungs can be affected by the inhalation manoeuvre used. Conventional in-vitro testing of the emitted dose from a dry powder inhaler (DPI) uses a vacuum pump to simulate an inhalation. We have adapted this method by replacing the pump with patient inhalation profiles and an anatomical throat. Three anatomical throat sizes and three inhalation profiles were used. The profiles represented the 10th, 50th and 90th percentiles of peak inhalation flow and acceleration of flow from a population of 50 COPD patients inhaling through empty Spiromax and Turbuhaler devices. Combining the dose emission results for the three throat sizes, the mean (SD) budesonide fine-particle dose (FPD) from budesonide-formoterol Spiromax 320/9 μg was 78.91 (20.18), 79.91 (15.36) and 75.10 (19.91)μg and the total emitted dose (TED) of budesonide was 263.69 (40.74), 261.20 (21.65) and 261.61 (45.65)μg. Similarly, the FPD from 320/9 μg Turbuhaler was 22.45 (3.24), 52.20 (12.57) and 69.11 (75.10)μg with a TED of 143.80 (14.90), 149.50 (26.61) and 158.61 (43.04)μg. Spiromax showed greater consistency than Turbuhaler over a range of inspiratory flow profiles. The results demonstrate the value of this new method to assess the doses that patients receive during real-life use of their DPI.
authors.affiliation: RiRL, 5a Coles Lane, Oakington, Cambridge, UK. Electronic address: h.chrystyn@gmail.com.
authors.forename: Henry
authors.initials: H
authors.lastname: Chrystyn
authors.affiliation: Medical Affairs, Teva Pharmaceuticals, Helsingborg, Sweden. Electronic address: guilherme.safioti@teva.se.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Safioti
authors.affiliation: Global Respiratory R&D, Teva Pharmachemie, Haarlem, The Netherlands. Electronic address: hans.keegstra@tevapharmachemie.com.
authors.forename: Johan René
authors.initials: JR
authors.lastname: Keegstra
authors.affiliation: Global Medical Affairs, Teva Pharmaceuticals, Malvern, PA, USA. Electronic address: gokul.gopalan@tevapharm.com.
authors.forename: Gokul
authors.initials: G
authors.lastname: Gopalan
mesh_terms: D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D058995:Dry Powder Inhalers; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008953:Models, Anatomic; D010316:Particle Size; D010614:Pharynx / Q000033:anatomy & histology* / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy
chemical_list: D001993:Bronchodilator Agents; D019819:Budesonide; D000068759:Formoterol Fumarate
keywords: Anatomical throat; Chronic obstructive pulmonary disease; Dose constancy; Dry powder inhaler; Inhalation manoeuvre; Inhalation profile