Lung Deposition of Fenoterol and Flunisolide Delivered Using a Novel Device for Inhaled Medicines: Conclusion

Lung Deposition of Fenoterol and Flunisolide Delivered Using a Novel Device for Inhaled Medicines: ConclusionLarge particles or droplets delivered from inhaler devices will be deposited in the oropharynx, possibly contributing to unwanted side effects, but making no contribution to clinical efficacy. The addition of baffles to inhaler devices reduces oropharyngeal deposition, but may also reduce drug delivery to the lungs. Modification of the RESPIMAT by addition of a baffle in the mouthpiece reduced oropharyngeal deposition from 26.2 to 7.8% of the dose, and reduced whole lung deposition from 44.6 to 29.5%, with the overall effect that targeting of delivered drug to the lungs was improved by the baffle. Here This improvement in the selectivity of drug delivery for the RESPIMAT with baffle could result in a reduction in both the local and systemic side effects of high dose inhaled corticosteroids.
The percentage of the dose of flunisolide in the exhaled air was significantly greater for the RESPIMAT and RESPIMAT with baffle than for the MDI with spacer (12.4% and 7.4% vs 0.4%, respectively). This reflects the high proportion of small, rapidly evaporating ethanol droplets in the RESPIMAT flunisolide formulation which, despite a 10-s breath-holding pause, did not deposit by sedimentation in the airways. Most of the radioactivity in the exhaled air was on the exhalation filter, with only a very small proportion being detected on the nose plugs.
It is a possibility that the additives, including ethanol, in aerosol formulations can cause broncho-constriction in some patients with asthma. The RESPIMAT is a multidose device and the fenoterol solution for inhalation contains the preservative ben-zalkonium chloride. This additive has been shown to cause bronchospasm in some asthmatic patients. However, in the present studies, no paradoxical bronchoconstriction was noted with either drug formulation in any of the healthy volunteers.
In summary, the results from these studies indicate that the RESPIMAT device may prove to be an effective alternative to MDIs for administration of bronchodilator and anti-inflammatory agents in the therapy of asthma and COPD. Improved lung targeting achieved by the RESPIMAT may permit asthma to be treated with a lower daily dose of drug compared with those given by MDI. In patients requiring treatment with high-dose inhaled corticosteroids, where local and systemic side effects are of major concern, the reduced oropharyngeal deposition with the RESPIMAT (baffle) system may be a particularly useful option. Future research should address the effectiveness, side effects, and acceptability of this delivery system, not only in patients with asthma, but also in those with COPD.

Category: Lung Deposition

Tags: fenoterol, flunisolide, gamma scintigraphy, inhaler devices, lung deposition, oropharyngeal deposition