Validation of a new breathing simulator generating and measuring inhaled aerosol with adult breathing patterns

The use of breathing simulators for the in vitro determination of the inhal ed mass of drug from nebulizers has become widely accepted. Their use is, h owever, based on the assumption that there is a correlation between the in vitro and in vivo inhaled mass of drug. The aim of the study was therefore to investigate whether a new breathing simulator-the MIMIC Breathing Emulat or (Medic-Aid Limited, Bognor Regis, UK)-could accurately emulate the in: v ivo inhaled mass of budesonide suspension for nebulization. Eight adult hea lthy subjects were included. Each subject inhaled for 2 min from a Spira Mo dule 1 jet nebulizer (Respiratory Care Center, Hameenlinna, Finland), charg ed with 1.0 mg of budesonide suspension for nebulization (0.5 mg mL(-1), 2 mt suspension, AstraZeneca, Sweden) and supplied with an inhaled mass filte r between the nebulizer and the subject. The breathing patterns were record ed during the nebulization and simulated in vitro at two different experime ntal sites (simulations A and B) with the breathing simulator. With the pat ients breathing through the filters (in vivo test), inhaled mass of budeson ide averaged 103.6 mu g. The two in vitro experiments using the simulator r evealed similar results with in vitro simulation A equal to 101.0 mu g and simulation B 99.1 mu g. There were no statistically significant differences between the in vivo results and those of in vitro simulation A. Results we re significantly different for simulation B (p = 0.032) although the differ ence was less than 4.5%. These data indicate that the breathing simulator c an be used to accurately simulate sine waveforms, human breathing patterns, and the in vitro and in vivo inhaled mass of budesonide suspension for neb ulization.