title: An insight into powder entrainment and drug delivery mechanisms from a modified Rotahaler®.
abstract: This study aims to improve understanding of the powder fluidisation and aerosolisation processes unique to a split capsule dry powder inhaler. It uses a combination of dynamic real-time methods and a suite of powder material physicochemical characterisation methods. The study focused on examining the effect of different characteristics of lactose carrier employed, and considered specifically the powder fluidisation, entrainment and de-agglomeration mechanisms. A GSK Rotahaler(®) was selected as the inhaler device. Powder fluidisation and entrainment were investigated using the ensemble technique of laser diffraction and high-speed imaging. This ensemble technique afforded both the powder entrainment profile and simultaneous visual confirmation of the capsule movement and powder fluidisation within the Rotahaler. The results showed that powder fluidisation from a dynamic split capsule was substantially different to that from a static powder bed. Furthermore, the presence of the split capsule dominated powder emission mechanisms from the Rotahaler, regulated by its impaction on the grid/Rotahaler wall and the rotational movement in the entrained air. Of all the material characterisation metrics, the most significant linear correlation was revealed between powder permeability and the aerosolisation efficiency as measured by fine particle fraction (R(2)=0.98). This indicates that drug delivery from the Rotahaler was mainly governed by the influence of the cohesive fine particle size component. Powder permeability as a practical test may afford an effective and practical predictive link between the raw excipients and drug delivery performance from the capsule device.
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Sim
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Margo
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia; Global Manufacture and Supply, GlaxoSmithKline, Boronia, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Parks
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Howell
authors.affiliation: DFE Pharma, Klever Strasse 187, D-47574, Goch, Germany.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Hebbink
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Orlando
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia; Global Manufacture and Supply, GlaxoSmithKline, Boronia, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Leslie
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Ho
authors.affiliation: MIPS/GSK Centre of Innovation, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: david.morton@monash.edu.
authors.forename: David A V
authors.initials: DA
authors.lastname: Morton
mesh_terms: D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D058995:Dry Powder Inhalers / Q000592:standards*; D007785:Lactose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008962:Models, Theoretical; D010316:Particle Size; D011208:Powders; D013499:Surface Properties
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D007785:Lactose; D000420:Albuterol
keywords: Dry powder inhalation; Entrainment; Fluidisation; High-speed imaging; Lactose; Rotahaler(®)