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~90 L . 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 mg 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 . min -1 , comparable to that for the Turbuhaler (58 L . min ) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L . min -1 or 54 L . 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. Eur Respir J 2000; 16: 178±183.
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.
Our objective was to assess the deposition and pharmacokinetics of a novel formulation of flunisolide (Aerobid, Forest Laboratories) in hydrofluoroalkane (HFA) 134a delivered by pressurized metered dose inhaler (pMDI). The design was a two-way crossover investigation in 12 healthy male subjects comparing HFA-134a flunisolide by pMDI versus pMDI plus 50 mL spacer device. Four of these subjects also took part in a two-way crossover investigation comparing chlorofluorocarbon (CFC) flunisolide pMDI versus pMDI plus Aerochamber holding chamber. The imaging technique of gamma scintigraphy was used to quantify total and regional lung deposition of flunisolide. Plasma levels of flunisolide and its major metabolite (6beta-OH flunisolide) were also determined. The spacer and Aerochamber reduced oropharyngeal deposition dramatically for both the HFA and CFC products (mean 59.8 to 14.9% (p < 0.01) of ex-valve (metered) dose for HFA product; 66.3 to 12.3% (p < 0.01) of ex-valve dose for CFC product) owing to deposition of part of the dose on the walls of the add-on devices themselves. Lung deposition averaged 22.6 and 40.4% (p < 0.01) of the ex-valve dose for the HFA formulation used with pMDI alone and with pMDI plus spacer. Mean lung deposition of the CFC formulation delivered via the Aerochamber (mean 23.4%) was higher than that for the CFC pMDI alone (mean 17.0%), but this difference was not statistically significant. Lung deposition expressed as percentage ex-device (delivered) dose averaged 68.3% for HFA pMDI plus spacer and 19.7% for CFC pMDI. Plasma levels of flunisolide were higher for the pMDI plus spacer than for pMDI alone, reflecting higher lung deposition via the spacer, but plasma levels of the 6beta-OH flunisolide metabolite were higher for the pMDI alone as a consequence of higher oropharyngeal deposition. When delivered via the spacer, pulmonary targeting of the flunisolide HFA formulation was improved compared with the CFC formulation, which should benefit patients by providing satisfactory asthma therapy from a much-reduced delivered dose of flunisolide.
The study showed no difference in pharmacokinetic profiles between the various aerosol dosage forms. pH of the aqueous solutions did not affect kinetics or relative bioavailability.
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