1998 OPEN FORUM Abstracts
VARIABILITY IN ALBUTEROL DELIVERY WITH PROVENTIL HFA AND VENTOLIN METERED DOSE INHALERS (MDIs).
Ralph A. Lugo, PharmD, Jim Keenan, BS, RRT, Robert M. Ward, MD, John W. Salyer, BS, RRT. Primary Children's Medical Center and the University of Utah College of Pharmacy, Salt Lake City, Utah.
Introduction: Aerosolized albuterol (ALB) is commonly administered via MDI and in-line spacer to mechanically ventilated patients. CFC-free Proventil HFA (Key Pharmaceuticals) is now available, however its unique canister and stem design was not intended for use with in-line spacers. This canister-spacer incompatibility appears to result in significant variability in the visible quality of aerosol cloud formation when used with the ACE spacer. This is apparent upon repeated actuation and may result from imprecise drug release from the valve. Furthermore, poor aerosol cloud formation may result in greater impaction on the spacer, thereby reducing drug delivery to the patient. The objective of this study was to determine the precision (variability) of ALB release from Proventil HFA and compare it to Ventolin (Glaxo Wellcome). In addition, we sought to compare ALB impaction in the spacers following actuation. Methods: The ALB recovery model consisted of a Sims filter (#2832) attached to the patient end of an ACE spacer. Continuous negative pressure (-100 mm Hg) was applied to the open end of the filter. Thus, aerosolized ALB flowed unidirectionally from the spacer to the filter following each MDI actuation. Each experiment was conducted by actuating a single MDI into an ACE spacer. One minute following actuation, the spacer and filter were rinsed with 20 mL and 45 mL of filtered water, respectively. Ten replicates were performed for each of the two brands of MDIs. Different canisters were used for each replicate. ALB concentrations in the resultant solutions were assayed using high performance liquid chromatography. We validated this methodology and assay by determining recovery of a known quantity of ALB placed on five filters. Mean recovery was 97.2% ± 3.0%. All data are reported as mean percent of the labeled amount of ALB released with each actuation (100 mcg) ± standard deviation. Results: Total ALB recovery for both Proventil HFA and Ventolin were highly variable and ALB delivery commonly exceeded the labeled dose. Proventil HFA had a slightly larger standard deviation and range of recovery; however, there was no statistically significant difference between the two MDIs (p>0.05, Student t-test). Furthermore, the 2 groups did not differ in spacer impaction of aerosol (p>0.05, Student t-test).
Filter Spacer Total Recovery
Proventil HFA 59.0%(22.4%) 40.9%(11.4%) 99.9%(27.7%)
Ventolin 69.7%(12.2%) 38.9%(12.5%) 108.6%(22.1%)
Proventil HFA 47.3-135.4%
Conclusion: Despite the visually apparent variability in aerosol cloud formation when Proventil HFA is actuated into an ACE spacer, total ALB recovery and drug impaction on the spacer did not differ from Ventolin. However, it is clinically important to recognize that there is large variation in total ALB delivery from both MDIs when used with an ACE spacer. This may result in variability in therapeutic response necessitating close patient monitoring and dose titration.
The 44th International Respiratory Congress Abstracts-On-Disk®, November 7 - 10, 1998, Atlanta, Georgia.