The Science Journal of the American Association for Respiratory Care

2008 OPEN FORUM Abstracts

IN VITRO COMPARISON OF TWO NEBULIZER/COMPRESSOR SYSTEMS ON THE EMITTED DOSE OF NEBULIZED RACEMIC FORMOTEROL AND ARFORMOTEROL

Andrea Bauer1, Paul McGlynn1, Michelle Otte2, Sejal Patel2, Lisa Curry1, John Hanrahan1



Background: Two nebulized long-acting β2-agonists (LABAs), racemic formoterol and rformoterol (the R,R-formoterol isomer) are approved for treating COPD. These LABAs are recommended to be administered by the Pari LC Plus®/ Pari Proneb and Ultra the Pari LC Plus®/ Pari Duraneb® 3000 nebulizer/compressor systems, respectively. Drug formulation and nebulizer/compressor systems can influence the amount of drug delivered, and consequently treatment outcomes. This study compared the delivered dose of nebulized racemic formoterol fumarate (17 μg/2mL) and arformoterol (15μg/2mL) by two different nebulizer/compressor systems.

Methods: Breath simulation parameters were selected to represent what might be observed in COPD patients (tidal volume = 500mL, I:E Ratio 1:2.3, BPM 12). The dose of arformoterol or formoterol on the inspiratory filters (Respirgard® II) was measured after a 12-minute nebulization period using the Pari LC Plus/Pari Trek® S and the Pari LC Plus®/Pari Proneb® Ultra II systems for each drug. Each experiment was repeated twice with each of 5 different nebulizers. In continuous nebulization experiments (i.e. no breathing pattern),, the delivered dose was collected in a glass Dreschel-type apparatus over both 6-minute and 9-minute nebulization periods. For each set of nebulizer/compressor experiments two different compressors and 5 different nebulizers were used (n=10). The fine droplet fraction (FDF) of the emitted dose was assessed by Andersen cascade impaction (ACI). All samples were analyzed by HPLC.

Results: Both nebulizer/compressor systems delivered a similar percent of nominal dose for each drug. The emitted amount of (R,R)-formoterol for arformoterol was approximately twice that of racemic formoterol, for both the breath simulation and continuous nebulization experiments (Table 1). The fine droplet fraction (FDF) for each compressor/nebulizer system was similar for each drug.

Conclusion: In this study approximately a 2-fold greater amount of the active (R,R)-formoterol was delivered by both nebulizer compressor systems of arformoterol (15μg/2mL) compared with racemic formoterol (17μg/2mL ). Emitted dose amounts did not appreciably differ between 6 and 9 minute total nebulization time periods. The amount of FDF did not differ by drug formulation or nebulizer/compressor system. Support provided by Sepracor Inc.