title: Evaluation and modification of commercial dry powder inhalers for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation.
abstract: The aim of this study was to evaluate and modify commercial dry powder inhalers (DPIs) for the aerosolization of a submicrometer excipient enhanced growth (EEG) formulation. The optimized device and formulation combination was then tested in a realistic in vitro mouth-throat - tracheobronchial (MT-TB) model. An optimized EEG submicrometer powder formulation, consisting of albuterol sulfate (drug), mannitol (hygroscopic excipient), l-leucine (dispersion enhancer) and poloxamer 188 (surfactant) in a ratio of 30:48:20:2 was prepared using a Büchi Nano spray dryer. The aerosolization performance of the EEG formulation was evaluated with five conventional DPIs: Aerolizer, Novolizer, HandiHaler, Exubera and Spiros. To improve powder dispersion, the HandiHaler was modified with novel mouth piece (MP) designs. The aerosol performance of each device was assessed using a next generation impactor (NGI) at airflow rates generating a pressure drop of 4 kPa across the DPI. In silico and in vitro deposition and hygroscopic growth of formulations was studied using a MT-TB airway geometry model. Both HandiHaler and Aerolizer produced high emitted doses (EDs) together with a significant submicrometer aerosol fraction. A modified HandiHaler with a MP including a three-dimensional (3D) array of rods (HH-3D) produced a submicrometer particle fraction of 38.8% with a conventional fine particle fraction (%<5 μm) of 97.3%. The mass median diameter (MMD) of the aerosol was reduced below 1 μm using this HH-3D DPI. The aerosol generated from the modified HandiHaler increased to micrometer size (2.8 μm) suitable for pulmonary deposition, when exposed to simulated respiratory conditions, with negligible mouth-throat (MT) deposition (2.6%).
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298-0533, USA.
authors.forename: Yoen-Ju
authors.initials: YJ
authors.lastname: Son
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000336:Aerosols; D000420:Albuterol / Q000737:chemistry; D001993:Bronchodilator Agents / Q000737:chemistry; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry*; D007930:Leucine / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D008353:Mannitol; D007930:Leucine; D000420:Albuterol