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J Aerosol Med. 2007 Spring;20(1):75-82.

The effect of biphasic inhalation profiles on the deposition and clearance of coarse (6.5 microm) bolus aerosols.

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1
Nektar Therapeutics, San Carlos, California, USA. aclark@ca.nektar.com

Abstract

The influence of particle size upon deposition in the human airways is well understood. Pharmaceutical aerosol formulators strive to generate fine aerosols with the potential to penetrate into the deep lung. However, flow rate can also have a major influence on deposition, particularly with coarse aerosols. This study investigated the use of biphasic flow profiles with low flow in the proximal conducting airway as a means of effecting efficient delivery of a coarse aerosol. The study shows that 6.5-microm MMAD aerosol droplets can be deposited in the lung with high efficiency. The delivery technique achieved greater than 70% of the inhaled dose deposited in the whole lung and greater than 50% deposited in the lung periphery. Furthermore, the biphasic flow profiles used, with initial low flow segments of between 300 mL and 900 mL inhaled volume at 8 L/min, are practical flow regimens that should be acceptable to patients and that can be applied to single-breath dry powder inhalers. Twenty-four-hour clearance and Penetration Index measurements were used as a marker for peripheral deposition, and the data show a clear correlation between Penetration Index and 24-h retention.

PMID:
17388755
DOI:
10.1089/jam.2006.0557
[Indexed for MEDLINE]
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