title: Exploring the impact of sample flowrate on in vitro measurements of metered dose inhaler performance.
abstract: Pharmacopoeial methods for measurement of the aerodynamic particle size distribution (APSD) of metered dose inhalers (MDIs) by cascade impaction specify a sampling flow rate of 28.3L/min. However, there is little data within the literature to rationalize this figure, or to support its clinical relevance. In addition, the standard United States Pharmacopoeia Induction Port (USP IP) used for testing is known to inaccurately reflect deposition behavior in the upper airway, further compromising the relevance of testing, for product development. This article describes experimental studies of the effect of sampling flow rate on APSD data gathered using an Andersen Cascade Impactor (ACI). Tests were carried out using two different formulations to assess the influence of formulation composition. In addition, comparative testing with an Alberta Idealised Throat, in place of the USP IP, to ensure more realistic representation of the upper airway. The results show how measured APSD and fine particle dose, the dose than on the basis of size would be expected to deposit in the lung, vary as a function of test methodology, providing insight as to how the testing can be modified towards greater clinical relevance.
authors.affiliation: Chiesi Ltd., Bath Rd. Ind. Est., Chippenham, Wiltshire SN14 0AB, UK. Electronic address: d.lewis@chiesi.com.
authors.forename: D A
authors.initials: DA
authors.lastname: Lewis
authors.affiliation: Chiesi Ltd., Bath Rd. Ind. Est., Chippenham, Wiltshire SN14 0AB, UK.
authors.forename: H
authors.initials: H
authors.lastname: O'Shea
authors.affiliation: Chiesi Ltd., Bath Rd. Ind. Est., Chippenham, Wiltshire SN14 0AB, UK.
authors.forename: T K
authors.initials: TK
authors.lastname: Church
authors.affiliation: Chiesi Ltd., Bath Rd. Ind. Est., Chippenham, Wiltshire SN14 0AB, UK.
authors.forename: G
authors.initials: G
authors.lastname: Brambilla
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 2006, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Traini
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, The University of Sydney, 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 2006, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Young
mesh_terms: D000280:Administration, Inhalation; D004339:Drug Compounding; D004867:Equipment Design; D006801:Humans; D036501:Metered Dose Inhalers / Q000592:standards*; D010316:Particle Size; D012212:Rheology / Q000295:instrumentation*
keywords: Aerodynamic particle size distribution; Alberta idealized throat; Cascade impactor; Fine particle dose; Metered dose inhalers; Testing conditions