The effect of ethanol on the formation and physico-chemical properties of particles generated from budesonide solution-based pressurized metered-dose inhalers.

The aerosol performance of budesonide solution-based pressurized metered-dose inhalers (HFA 134a), with various amounts of ethanol (5-30%, w/w) as co-solvents, was evaluated using impaction and laser diffraction techniques. With the increase of ethanol concentration in a formulation, the mass median aerodynamic diameter was increased and the fine particle fraction showed a significant decline. Although data obtained from laser diffraction oversized that of the impaction measurements, good correlations were established between the two sets of data. Particles emitted from all the five formulations in this study were amorphous, with two different types of morphology - the majority had a smooth surface with a solid core and the others were internally porous with coral-like surface morphology. The addition of ethanol in the formulation decreased the percentage of such irregular-shape particles from 52% to 2.5% approximately, when the ethanol concentration was increased from 5% to 30%, respectively. A hypothesis regarding the possible particle formation mechanisms was also established. Due to the difference of droplet composition from the designed formulation during the atomization process, the two types of particle may have gone through distinct drying processes: both droplets will have a very short period of co-evaporation, droplets with less ethanol may be dried during such period; while the droplets containing more ethanol will undergo an extra condensation stage before the final particle formation.