2005 OPEN FORUM Abstracts
Delivery of Ventavis (iloprost) Inhalation Solution with HaloLiteT, ProdoseT and I-nebT Adaptive Aerosol Delivery (AAD)® systems - an in vitro study
Van Dyke R1 , Nikander K2
1CoTherix, South San Francisco, CA; 2Respironics RDD Division, Cedar Grove, NJ
Ventavis (iloprost) Inhalation Solution (2 mL, 10µg/mL, CoTherix) is approved in doses of either 2.5µg or 5.0µg for the treatment of pulmonary arterial hypertension (WHO Group I) in patients with NYHA Class III or IV symptoms. The AAD systems are breath-actuated devices that pulse aerosol into the first part of the patient's inspiration. Prodose is currently the only recommended drug delivery device for use with Ventavis. We have characterized in vitro the Mass Median Aerodynamic Diameter (MMAD) and Fine Particle Fraction (FPF) of iloprost when delivered via the HaloLite, Prodose and I-neb AAD systems. HaloLite was the first generation AAD device used in the Phase III pivotal study of inhaled iloprost in patients with PAH, and I-neb is the 3rd generation AAD system.
To analyze both the MMAD and FPF, the breath-actuated devices were connected to an Anderson cascade impactor which was connected to both a vacuum pump operating at a flow of 28.3 L/min and pressurized air. Air flow was regulated to the system with flow control valves to provide inhalation and exhalation flow to the devices. Approximately 4 liters of air was provided for each inhalation to allow complete deposition of aerosol to all stages of the impactor. Iloprost-specific HPLC analysis was used to quantify iloprost on impactor stages and filters.
The MMADs of the three devices - HaloLite, Prodose and I-neb - were 1.4 µm, 1.7 µm, and 2.1 µm, respectively. This low particle size is associated with alveolar deposition, which is desirable for local administration of this potent vasodilator to the pulmonary arterial bed. The FPFs (< 4.7 µm) were 91%, 82% and 82%, respectively.
The in vitro data demonstrates that all three AAD systems can deliver aerosols of Ventavis (iloprost) Inhalation Solution with comparable particle size distributions and very high Fine Particle Fractions.