Nasal Sound-Detected Breathing-Triggered Nebulizer Enhances Drug Delivery and Reduces Environmental Exposure in a Clinical Pharmacokinetic Study

Abstract

Background: Nebulizers utilize various aerosol-generating mechanisms. Recently, breath-actuated nebulizers have emerged to optimize delivery efficiency and reduce medication waste. However, their consistent and reliable inhalation triggering regarding uncertainties in aerosol drug absorption remains controversial for clinical use. We have developed a nasal sound-detected breathing-triggered mesh nebulizer that demonstrated enhanced drug delivery efficacy in in-vitro and ex-vivo studies. The current study aimed to compare this breathing-triggered mesh nebulizer with a continuous mesh nebulizer through a pharmacokinetic study involving healthy volunteers and assess environmental aerosol counts.

Methods: This was a crossover prospective clinical study (NCT06157515). Single salbutamol doses (2,500 μg) were administered using breath-triggered and continuous nebulizers, with a 1-week washout period. Delivery efficacy was assessed by measuring urine salbutamol concentration 30 min before/after inhalation and 24 h post-nebulization using high-performance liquid chromatography. Drug side effects, such as changes in heart rate, blood pressure, and other symptoms, were monitored. Fugitive aerosol concentrations in the environment were measured by aerodynamic particle sizers (APS) at 1-meter distances. Statistical analysis was conducted using paired t-tests, with significance set at P < .05.

Results: Twenty-four healthy volunteers with a mean age of 35 (± 10) y completed the study. No significant differences were observed in demographics and lung function tests. The baseline salbutamol urine concentrations were similar between the two nebulizers (P = .89). However, after 30 min, the nasal sound-detected trigger nebulizer showed a significantly higher salbutamol concentration (P < 0.05), a 1.8-fold increase over the continuous nebulizer. Despite higher drug absorption, vital signs remained stable with both nebulizers. No significant difference in 24-h metabolized salbutamol in urine (P = .82). Environmental aerosol concentration during inhalation indicated the continuous nebulizer released a significantly greater fugitive aerosol, approximately 5.2-fold higher than breath-triggered nebulization.

Conclusions: The nasal sound-detected breathing-triggered nebulizer demonstrated increased pulmonary drug delivery and reduced environmental drug waste compared to continuous nebulization, suggesting a more reliable and efficient option for clinical use.