In Vitro Determination of Inhaled Mass and Particle Distribution for Budesonide Nebulizing Suspension

ABSTRACT

Nebulized delivery of aerosols to the lung is a complex process dependent on the device, the drug preparation, the patient's breathing pattern and other factors. It is difficult to predict drug delivery in advance and most delivery systems are studied empirically on the bench. To standardize the delivery of aerosolized budesonide suspension, we measured the quantity of drug delivered to the patient mouthpiece using a piston pump as a model of patient breathing and absolute filters. The mass of aerosol at the mouthpiece (the "inhaled mass") was determined by high-pressure liquid chromatography (HPLC). The aerodynamic properties of the nebulized budesonide particles were determined by cascade impaction and HPLC. Because the drug is used to treat children, the bench model was based on a "pediatric" breathing pattern, that is, a tidal volume of 200 mL, a breathing frequency of 25 per minute, and a duty cycle of 0.5. Twenty-seven nebulizer/compressor combinations were studied. Inhaled mass varied over a large range (2%–18% of the nebulizer charge or 20–180 μg of budesonide). In the 13 most efficient systems, the mass median aerodynamic diameter (MMAD) varied from (3.8–5.5 μm). Clinical reliability in day-to-day use for one of the most efficient nebulizer/compressor systems (Pari LC-Jet Plus/Pari Master, PARI Respiratory Equipment Inc., Richmond, VA) was simulated by a protocol involving repeated nebulization and washing (58 runs). There were no statistically significant changes in inhaled mass or MMAD throughout the washing protocol. Finally, differences between the more efficient nebulizers were minimized by correcting inhaled mass for the "respirable mass," a calculation designed to estimate delivery to the lower respiratory tract. Values of respirable mass for the most efficient nebulizers approximated 10% of the nebulizer charge or 100 μg of budesonide. In conclusion, budesonide suspension can be efficiently nebulized with MMAD suitable for treatment of the lower respiratory tract, but each system must be tested before consideration for a clinical trial. The Pari LC-Jet Plus nebulizer can be used repeatedly without a loss in efficiency.