"Evaluation of Efficacy and Clinical Pharmacokinetic Parameters of Different Nebulization Modes"

Study Design and Participants This study was designed to evaluate the performance of the proposed nebulizer mode converter using both in-vitro and ex-vivo models. The study involved healthy adult volunteers who provided informed consent before participating in the study. The aim was to assess drug delivery efficiency and medication wastage when using conventional jet nebulizers (JNs) compared to the modified nebulization system incorporating the mode converter. Each participant received the inhaled medication via both modes of nebulization-continuous jet nebulization and intermittent nebulization facilitated by the mode converter to allow for a direct comparison of drug deposition efficiency and aerosol delivery.

Experimental Models Two experimental setups were utilized: an in-vitro model employing a breathing simulator and an ex-vivo model involving human volunteers. The in-vitro model used a high-fidelity breathing simulator programmed to replicate a standardized adult respiratory pattern. The simulator was set to an inhalation-to-exhalation (I:E) ratio of 1:2, a respiratory rate of 20 breaths per minute, and a tidal volume of 500 mL. The inhaled drug dose, residual drug volume within the nebulizer chamber, and deposition of salbutamol sulfate within the delivery tubing (connection tube used to connect the jet nebulizer with the filter, which is used for collection of delivered aerosols) were measured to assess efficiency. In the ex-vivo model, each volunteer inhaled the aerosolized medication while an inhalation filter was placed between the nebulizer and the subject's airway to collect the delivered drug. As with the in-vitro model, residual drug amounts within the nebulizer chamber and salbutamol sulfate deposition within the delivery tubing were also measured. This setup enabled direct assessment of the proportion of medication that reached the subject's respiratory tract under both continuous and intermittent nebulization conditions. To ensure the reliability of results, each nebulization mode underwent ten repeated runs in both models. A jet nebulizer of the same commercial model was used for all in-vitro and ex-vivo experiments to maintain consistency and eliminate variability associated with differences between individual nebulizers. Experiments were conducted under normal ambient laboratory conditions, with room temperature maintained at 22-24 °C and relative humidity between 40-55%.

The experimental model setup was designed to evaluate the performance of the nebulization mode converter in comparison to conventional continuous nebulization. The system consisted of a standard jet nebulizer (Planet Health Wheeze nebulizer, Planet Health, Vapo Healthcare Co., Ltd, China), a breathing simulator (5600i, Michigan Instruments, USA), and an intermittent aerosol converter device (EGPO-SES, EG/P/2025/361).[1] Three distinct configurations were examined to assess aerosol generation and delivery under different operating conditions (Figure 1). In the ex-vivo model, the intermittent aerosol converter did not rely on flow-triggered breath sensing. Instead, the inspiratory and expiratory durations of each subject were measured using the Certifier FA Plus and used to set a time-based cycling pattern in which the converter switched on during the subject's inhalation interval (allowing passage of compressed air to the nebulizer head) and off during the exhalation interval. Both inhalation and exhalation times were fully adjustable by the subject, who could reset these intervals at any time to match changes in their spontaneous breathing pattern. The device also produced a fine click sound when transitioning between inhalation and exhalation phases, providing an audible cue that helped the subject maintain synchronization with the intermittent aerosol release.

In the clinical (ex-vivo) model, the inspiratory-to-expiratory (I:E) ratio was determined using the Certifier FA Plus high-flow analyzer (TSI Incorporated, USA). This device provides real-time respiratory measurements, including inspiratory time, expiratory time, and overall breathing cycle parameters. It was used to precisely determine the I:E ratio in volunteers receiving nebulized therapy, ensuring standardized respiratory conditions across all participants.

To ensure accuracy and consistency, the I:E ratio was measured multiple times for each participant, with the means of the most stable readings being used for data analysis. These measurements were critical in evaluating the synchronization of aerosol generation with the inhalation phase when using the nebulization mode converter. The recorded I:E ratios were then used to compare aerosol deposition efficiency between continuous and intermittent nebulization modes.