Elna B Berg1, Robert J Picard. 1. Analytical Development, AstraZeneca Research and Development, Scheelevägen 2 Lund SE-221 87 Sweden. elna.berg@astrazeneca.com
Abstract
BACKGROUND: An aerosol of budesonide inhalation suspension is delivered when used with various jet-nebulizer/compressor combinations. The constant introduction of new nebulizer/compressor combinations raises the question of whether the performance of these match the performance of existing devices. The aim of this study was to determine in vitro the inhaled mass and aerosol characteristics of budesonide inhalation suspension from a selection of jet-nebulizer/compressor combinations presently marketed in the United States, Europe, and Japan. METHODS: The in vitro characterization was performed using standardized and published methods. Each nebulizer was charged with 1 vial (2 mL) of budesonide inhalation suspension 0.25 mg/mL (0.5 mg budesonide) and run until end of aerosol formation. Droplet size and distribution was determined using a cooled impactor at air flow of 15 L/min. The inhaled mass of budesonide (ie, mass on the inhalation filter) was collected using a breathing simulator that mimicked the breathing patterns of an infant and a child. The aerosol was collected on filters placed between the nebulizer mouthpiece and the breathing simulator. Budesonide was quantified via standard high-performance liquid chromatography. RESULTS: The mass median aerodynamic diameter of the aerosol measured with the cooled impactor ranged between 4.8 mum and 9.9 mum, and the geometric standard deviation ranged between 1.7 mum and 2.1 mum. The inhaled mass of budesonide expressed as a percentage of the nebulizer charge ranged from 1% to 9% (infant) and from 4% to 20% (child). CONCLUSIONS: The in vitro budesonide mass collected on the inhalation filter and delivery characteristics differed considerably between the 30 nebulizer/compressor combinations. The present in vitro characterization of jet nebulizers can be used as a guidance for selection of jet-nebulizer/compressor combinations for delivery of the budesonide nebulization suspension in the home-care setting. Further investigations of new nebulizer/compressor combinations are warranted.
BACKGROUND: An aerosol of budesonide inhalation suspension is delivered when used with various jet-nebulizer/compressor combinations. The constant introduction of new nebulizer/compressor combinations raises the question of whether the performance of these match the performance of existing devices. The aim of this study was to determine in vitro the inhaled mass and aerosol characteristics of budesonide inhalation suspension from a selection of jet-nebulizer/compressor combinations presently marketed in the United States, Europe, and Japan. METHODS: The in vitro characterization was performed using standardized and published methods. Each nebulizer was charged with 1 vial (2 mL) of budesonide inhalation suspension 0.25 mg/mL (0.5 mg budesonide) and run until end of aerosol formation. Droplet size and distribution was determined using a cooled impactor at air flow of 15 L/min. The inhaled mass of budesonide (ie, mass on the inhalation filter) was collected using a breathing simulator that mimicked the breathing patterns of an infant and a child. The aerosol was collected on filters placed between the nebulizer mouthpiece and the breathing simulator. Budesonide was quantified via standard high-performance liquid chromatography. RESULTS: The mass median aerodynamic diameter of the aerosol measured with the cooled impactor ranged between 4.8 mum and 9.9 mum, and the geometric standard deviation ranged between 1.7 mum and 2.1 mum. The inhaled mass of budesonide expressed as a percentage of the nebulizer charge ranged from 1% to 9% (infant) and from 4% to 20% (child). CONCLUSIONS: The in vitro budesonide mass collected on the inhalation filter and delivery characteristics differed considerably between the 30 nebulizer/compressor combinations. The present in vitro characterization of jet nebulizers can be used as a guidance for selection of jet-nebulizer/compressor combinations for delivery of the budesonide nebulization suspension in the home-care setting. Further investigations of new nebulizer/compressor combinations are warranted.