title: Dose delivery characteristics of the AIR pulmonary delivery system over a range of inspiratory flow rates.
abstract: The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition.
authors.affiliation: Alkermes, Inc., 88 Sydney St., Cambridge, Massachusetts 02139, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: DeLong
authors.forename: Jim
authors.initials: J
authors.lastname: Wright
authors.forename: Mat
authors.initials: M
authors.lastname: Dawson
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Knut
authors.initials: K
authors.lastname: Sommerer
authors.forename: Craig
authors.initials: C
authors.lastname: Dunbar
mesh_terms: D000704:Analysis of Variance; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006801:Humans; D001239:Inhalation / Q000502:physiology*; D007320:Inspiratory Capacity / Q000502:physiology*; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D011208:Powders