ABSTRACT
Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often delivered via a large volume spacer device, but these are bulky and inconvenient. Dry powder inhalers (DPIs) provide a highly portable and convenient propellant-free alternative to pMDIs for asthma maintenance therapy However, each DPI could have unique in vivo delivery characteristcs. In order to quantify the total and regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b) Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized cross-over study was carried out in 12 mild to moderate asthmatic patients. Deposition was quantified by the imaging technique of gamma scintigraphy Optimal inhalation techniques were used throughout. Mean (SD) whole lung deposition (% metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2) %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P < 0.01]. The regional distribution patterns in the lungs were predominantly central for all three devices. Nebuhaler reduced oropharyngeal deposition significantly compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler and hence drugs delivered by Easyhaler would be expected to have a similar clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.
Subject(s)
Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Budesonide/administration & dosage , Nebulizers and Vaporizers/standards , Administration, Inhalation , Adolescent , Adult , Asthma/diagnostic imaging , Cross-Over Studies , Equipment Design , Female , Forced Expiratory Volume/drug effects , Humans , Male , Middle Aged , Peak Expiratory Flow Rate/drug effects , Powders , Radionuclide Imaging , Statistics, Nonparametric , Technetium , Treatment Outcome , Vital Capacity/drug effectsABSTRACT
Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been identified as being deleterious to the environment leading to a ban on their production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One disadvantage of DPIs is that in vivo lung deposition can be influenced by the patient's inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler (AM-MDPI) has been designed to offer low resistance on inhalation, so that asthmatic patients can achieve inhaled flow rates of approximately 90 L x min(-1). The aim of the study was to evaluate the in vivo deposition of budesonide from the AM-MDPI at different flow rates and to compare this with delivery from a Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized, crossover study in which 13 healthy volunteers inhaled a single 200 microg dose of radiolabelled budesonide on four separate occasions with a minimum 44-h washout period between dosings. At the lowest flow rate of 54 L x min(-1), comparable to that for the Turbuhaler (58 L x min(-1)), a similar percentage of the metered dose was delivered to the lung (AM-MDPI median 19.9%; Turbuhaler median 21.4%). At high flow rate (peak inspiratory flow rate 99 L x min(-1)) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L x min(-1) or 54 L x min(-1) (median 25.0% and 19.9% of metered dose, respectively), thus demonstrating flow rate dependence. The pattern of regional lung deposition from the AM-MDPI was similar for all three inhalation manoeuvres. It was concluded that the ASTA Medica multi-dose dry powder inhaler achieves at least as much deposition of budesonide in the lungs as a Turbuhaler when used at similar inspiratory flow rates.
