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2631501 
Journal Article 
Abstract 
An in vitro evaluation of the new 20 µg/ml iloprost inhalation solution formulation - emitted dose and aerosol droplet characteristics 
Van Dyke, R; Hurren, AJ; Metcalf, AP; Byrne, SM; Hardaker, LE 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A3334 
English 
WOS:000208771002445 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Iloprost inhalation solution has been available in the US since 2005 as a 10 µg/mL solution for the treatment of pulmonary arterial hypertension (WHO group I, New York Heart Association Functional Class III or IV symptoms). Currently, inhaled iloprost 10 µg/mL solution is administered 6 to 9 times a day with at least 2 hours between doses. Documented here, a more concentrated formulation of 20 µg/mL was recently approved by the FDA and has undergone in vitro evaluation, which could reduce treatment times by ~50% due to the lower inhaled volume needed to achieve a 5 µg dose.

Methods: Using in vitro methodologies mimicking patient breathing, the aerosols emitted by the nebulizer (I-neb AAD System, Respironics Respiratory Drug Delivery, Philips Home Healthcare Solutions, Parsippany, NJ) with the 10 and 20 µg/mL iloprost solutions were captured on filters (n=18). The methods used were identical to those previously reported and served to bridge to the output of the predicate device, Halolite. The amount of iloprost on the filters was quantified with iloprost-specific HPLC methodology. Aerosol droplet sizes and distributions for both solutions were obtained with an Andersen Cascade Impactor at 28.3 L/min flow rate and a simulated breathing pattern. Iloprost was extracted from impactor stages and quantified by HPLC.

Results: The mean ± SD emitted doses of iloprost were 4.54 ± 0.3 µg for the 10 µg/mL solution and 4.97 ± 0.2 µg for the 20 µg/mL solution. The in vitro nebulization times were 601 seconds for the 10 µg/mL solution and 229 seconds for the 20 µg/mL solution. The Mass Median Aerodynamic Diameters ± GSD of the iloprost inhalation solution droplets were 1.7 µm ± 1.5 for the 10 µg/mL solution and 1.9 µm ± 1.7 for the 20 µg/mL solution. The Fine Particle Fractions (percent of aerosol droplets <4.7 µm) were 95% and 90%, respectively.

Conclusions: The in vitro results indicate that the emitted doses and aerosol droplet characteristics were similar for iloprost 10 µg/mL solution and 20 µg/mL solution and should result in similar lung depositions. The perceived clinical benefits may include a reduction in time spent on the inhalation of iloprost and, as a consequence, possibly higher adherence to treatment. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010