Effects on Aerosol Performance of Mixing of Either Budesonide or Beclomethasone Dipropionate With Albuterol and Ipratropium Bromide

Abstract

BACKGROUND:

Mixing of nebulized drugs is common in real life, but its consequences on aerosol output and granulometry are poorly known.

METHODS:

In an in vitro study I evaluated the effects on aerosol output, drug output, and aerosol particle size characteristics of mixing either beclomethasone dipropionate or budesonide with albuterol and ipratropium bromide. I tested the SideStream and VentStream-Pro nebulizers, run with the AirClinic compressor. Using the same fill volume in all experiments, I nebulized and evaluated each studied drug alone, and 2 drug mixtures: beclomethasone plus albuterol plus ipratropium; and budesonide plus albuterol plus ipratropium. I measured aerosol output via gravimetrics. I measured drug delivery by collecting the aerosol on a filter in the inspiratory limb, and the residual solution in the reservoir and the circuit after nebulization, and assayed those liquids with chromatography. I measured particle size distribution via cascade impaction.

RESULTS:

Mixing tended to reduce drug output and to increase mass median aerodynamic diameter with the SideStream, but not always with the VentStream-Pro. However, the drug output always remained satisfactory and the mass median aerodynamic diameters were within the respirable range. When nebulized alone, the respirable mass of bronchodilators ranged from 18% to 40% of the nominal dose; when mixed, it ranged from 13% to 37%. When nebulized alone, the respirable mass of corticosteroids ranged from 10% to 24% of the nominal dose; when mixed, it ranged from 10% to 17%.

CONCLUSIONS:

Both the SideStream and VentStream-Pro have good aerosol performance in nebulizing budesonide or beclomethasone dipropionate alone, and when mixed with albuterol and ipratropium bromide.