In Vitro Tests for Aerosol Deposition. IV: Simulating Variations in Human Breath Profiles for Realistic DPI Testing

Area of Science:

• Pharmacology
• Biomedical Engineering
• Respiratory Medicine

Background:

• The total lung dose in vitro (TLDin vitro) represents drug aerosol passing through an in vitro mouth-throat model during inhalation.
• Selecting realistic inhalation profiles (IPs) is crucial for accurate in vitro testing of powder inhalers.

Purpose of the Study:

• To recommend a general method for selecting IPs for powder inhalers based on airflow resistance (R).
• To evaluate the impact of training and airflow resistance on inhalation variables.

Main Methods:

• A drug-free clinical trial with healthy adult volunteers was conducted.
• Inhalation profiles (IPs) were collected under varying airflow resistances and training levels.
• IP data were analyzed to understand population distributions and dependencies on training and resistance.

Main Results:

• Simulated IPs, including peak inspiratory flow rate (PIFR), were dependent on airflow resistance (R) and training.
• PIFR was inversely proportional to R, allowing PIFR calculation based on assigned R.
• Inhalation time and volume were independent of R but influenced by training.

Conclusions:

• Simulated IPs enhance the in vitro testing of dry powder inhalers (DPIs).
• This approach increases confidence in initiating clinical testing for new DPI devices.