Pascal Demoly1, Paul Hagedoorn2, Anne H de Boer2, Henderik W Frijlink2. 1. Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve and University Hospital of Montpellier, 371 Ave. du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Electronic address: pascal.demoly@inserm.fr. 2. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Abstract
BACKGROUND: Although understanding of the scientific basis of aerosol therapy with dry powder inhalers (DPIs) has increased, some misconceptions still persist. These include the beliefs that high resistance inhalers are unsuitable for some patients, that extra fine (<1.0 μm) particles improve peripheral lung deposition and that inhalers with flow rate-independent fine particle fractions (FPFs) produce a more consistent delivered dose to the lungs. OBJECTIVES: This article aims to clarify the complex inter-relationships between inhaler design and resistance, inspiratory flow rate (IFR), FPF, lung deposition and clinical outcomes, as a better understanding may result in a better choice of DPI for individual patients. METHODS: The various factors that determine the delivery of drug particles into the lungs are reviewed. These include aerodynamic particle size distribution, the inspiratory manoeuvre, airway geometry and the three basic principles that determine the site and extent of deposition: inertial impaction, sedimentation and diffusion. DPIs are classed as either dependent or independent of inspiratory flow rate and vary in their internal resistance to inspiration. The effects of these characteristics on drug deposition in the airways are described using data from studies directly comparing currently available inhaler devices. RESULTS: Clinical experience shows that most patients can use a high resistance DPI effectively, even during exacerbations. Particles in the aerodynamic size range from 1.5-5 μm are shown to be optimal, as particles <1.0 μm are very likely to be exhaled again while those >5 μm may impact on the oropharynx. For DPIs with a constant FPF at all flow rates, less of the delivered dose reaches the central and peripheral lung when the flow rate increases, risking under-dosing of the required medication. In contrast, flow rate-dependent inhalers increase their FPF output at higher flow rates, which compensates for the greater impaction on the upper airways as flow rate increases. CONCLUSIONS: The technical characteristics of different inhalers and the delivery and deposition of the fine particle dose to the lungs may be important additional considerations to help the physician to select the most appropriate device for the individual patient to optimise their treatment.
BACKGROUND: Although understanding of the scientific basis of aerosol therapy with dry powder inhalers (DPIs) has increased, some misconceptions still persist. These include the beliefs that high resistance inhalers are unsuitable for some patients, that extra fine (<1.0 μm) particles improve peripheral lung deposition and that inhalers with flow rate-independent fine particle fractions (FPFs) produce a more consistent delivered dose to the lungs. OBJECTIVES: This article aims to clarify the complex inter-relationships between inhaler design and resistance, inspiratory flow rate (IFR), FPF, lung deposition and clinical outcomes, as a better understanding may result in a better choice of DPI for individual patients. METHODS: The various factors that determine the delivery of drug particles into the lungs are reviewed. These include aerodynamic particle size distribution, the inspiratory manoeuvre, airway geometry and the three basic principles that determine the site and extent of deposition: inertial impaction, sedimentation and diffusion. DPIs are classed as either dependent or independent of inspiratory flow rate and vary in their internal resistance to inspiration. The effects of these characteristics on drug deposition in the airways are described using data from studies directly comparing currently available inhaler devices. RESULTS: Clinical experience shows that most patients can use a high resistance DPI effectively, even during exacerbations. Particles in the aerodynamic size range from 1.5-5 μm are shown to be optimal, as particles <1.0 μm are very likely to be exhaled again while those >5 μm may impact on the oropharynx. For DPIs with a constant FPF at all flow rates, less of the delivered dose reaches the central and peripheral lung when the flow rate increases, risking under-dosing of the required medication. In contrast, flow rate-dependent inhalers increase their FPF output at higher flow rates, which compensates for the greater impaction on the upper airways as flow rate increases. CONCLUSIONS: The technical characteristics of different inhalers and the delivery and deposition of the fine particle dose to the lungs may be important additional considerations to help the physician to select the most appropriate device for the individual patient to optimise their treatment.
Authors: Edward M Kerwin; Herminia Taveras; Harald Iverson; Denise Wayne; Tushar Shah; Mark S Lepore; David S Miller Journal: Clin Drug Investig Date: 2016-01 Impact factor: 2.859
Authors: M Luinstra; A W F Rutgers; H Dijkstra; F Grasmeijer; P Hagedoorn; J M J Vogelzang; H W Frijlink; A H de Boer Journal: PLoS One Date: 2015-07-14 Impact factor: 3.240