title: Dry powder inhaler device influence on carrier particle performance.
abstract: Dry powder inhalers (DPIs) are distinguished from one another by their unique device geometries, reflecting their distinct drug detachment mechanisms, which can be broadly classified into either aerodynamic or mechanical-based detachment forces. Accordingly, powder particles experience different aerodynamic and mechanical forces depending on the inhaler. However, the influence of carrier particle physical properties on the performance of DPIs with different dispersion mechanisms remains largely unexplored. Carrier particle trajectories through two commercial DPIs were modeled with computational fluid dynamics (CFD) and the results were compared with in vitro aerosol studies to assess the role of carrier particle size and shape on inhaler performance. Two percent (w/w) binary blends of budesonide with anhydrous and granulated lactose carriers ranging up to 300 μm were dispersed from both an Aerolizer® and Handihaler® through a cascade impactor at 60 L min(-1). For the simulations, carrier particles were modeled as spherical monodisperse populations with small (32 μm), medium (108 μm), and large (275 μm) particle diameters. CFD simulations revealed the average number of carrier particle-inhaler collisions increased with carrier particle size (2.3-4.0) in the Aerolizer®, reflecting the improved performance observed in vitro. Collisions within the Handihaler®, in contrast, were less frequent and generally independent of carrier particle size. The results demonstrate that the aerodynamic behavior of carrier particles varies markedly with both their physical properties and the inhalation device, significantly influencing the performance of a dry powder inhaler formulation.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA. mjdonovan@utexas.edu
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Donovan
authors.forename: Sin Hyen
authors.initials: SH
authors.lastname: Kim
authors.forename: Venkatramanan
authors.initials: V
authors.lastname: Raman
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Smyth
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000295:instrumentation*; D004867:Equipment Design; D057446:Hydrodynamics; D007785:Lactose / Q000737:chemistry; D010316:Particle Size
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D019819:Budesonide; D007785:Lactose