Predicting Inhaled Drug Dose Generated by Mesh Nebulizers.

Abstract

<b><i>Background:</i></b> The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. <b><i>Methods:</i></b> An <i>in vitro</i> model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns (<i>n</i> = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the <i>ex vivo</i> study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. <b><i>Results:</i></b> The <i>in vitro</i> model showed that the inspiratory time to total respiratory cycle time (<i>T_i</i>/<i>T</i>_total; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The <i>ex vivo</i> model showed that <i>T_i</i>/<i>T</i>_total was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the <i>ex vivo</i> model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. <b><i>Conclusions:</i></b> The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.