title: Understanding the Different Effects of Inhaler Design on the Aerosol Performance of Drug-Only and Carrier-Based DPI Formulations. Part 1: Grid Structure.
abstract: The design of a dry powder inhaler device has significant influence on aerosol performance; however, such influence may be different between the drug-only and carrier-based formulations. The present study aims to examine the potential difference on the dispersion between these distinct types of formulations, using Aerolizer(®) as a model inhaler with the original or modified (cross-grid) designs. A coupled CFD-discrete element method analysis was employed to determine the flow characteristics and particle impaction. Micronized salbutamol sulphate as a drug-only formulation and three lactose carrier-based formulations with various drug-to-carrier weight ratios 1:5, 1:10 and 1:100 were used. The in vitro aerosolization performance was assessed by a next-generation impactor operating at 100 L/min. Using the original device, FPFloaded was reduced from 47.5 ± 3.8% for the drug-only formulation to 31.8 ± 0.7%, 32.1 ± 0.7% and 12.9 ± 1.0% for the 1:5, 1:10 and 1:100 formulations, respectively. With the cross-grid design, powder-mouthpiece impaction was increased, which caused not only powder deagglomeration but also significant drug retention (doubling or more) in the mouthpiece, and the net result is a significant decrease in FPFloaded to 36.8 ± 1.2%, 20.9 ± 2.6% and 21.9 ± 1.5% for the drug-only, 1:5 and 1:10 formulations, respectively. In contrast, the FPFloaded of the 1:100 formulation remained the same at 12.1 ± 1.3%, indicating the increased mouthpiece drug retention was compensated by increased drug detachment from carriers caused by increased powder-mouthpiece impaction. In conclusion, this study has elucidated different effects and the mechanism on the aerosolization of varied dry powder inhaler formulations due to the grid design.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Cassandra Ming Shan
authors.initials: CMS
authors.lastname: Leung
authors.affiliation: Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing, 210096, China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, 47907-2091, USA.
authors.forename: Qi Tony
authors.initials: QT
authors.lastname: Zhou
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.|JHL Biotech Inc., Zhubei City, Hsinchu Country 302, Taiwan Republic of China.
authors.forename: John Gar Yan
authors.initials: JGY
authors.lastname: Chan
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Tang
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Siping
authors.initials: S
authors.lastname: Sun
authors.affiliation: School of Materials Science and Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Runyu
authors.initials: R
authors.lastname: Yang
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia. kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D032882:Comprehension; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000295:instrumentation*; D004867:Equipment Design / Q000295:instrumentation*
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D000420:Albuterol
keywords: carrier system; computational fluid dynamics; device design; dry powder inhaler; inhaler grid structure