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Updated: Mar 13, 2026

Intratracheal Administration of Dry Powder Formulation in Mice
Published on: July 25, 2020
A Novel In-Line Delivery System to Administer Dry Powder Mannitol to Mechanically Ventilated Patients
Benny Feng1, Patricia Tang1, Sharon Shui Yee Leung1
11 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney , Sydney, Australia .
Background:
Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol increases sputum clearance, and therefore, we developed a system to administer it to mechanically ventilated patients without disconnection from the ventilator.
Methods:
The inspiratory line from a ventilator was split by using a three-way valve into two parallel lines where one contains a humidifier for normal breathing cycle and the other line contains a dry powder inhaler (Osmohaler™). The inspiratory air went through the dry powder line and aerosolized the mannitol powder only when its administration to a patient is required. We determined the delivered dose and particle size distributions of emitted aerosols in vitro from 9.5 mm endotracheal and 7.5 mm tracheostomy tubes, with inspiratory airflow of 60, 70, and 80 L/min.
Results:
This novel setup was able to deliver 24.6% ± 3.33% of the 160 mg loaded dose mannitol powder (4 × 40 mg capsules) and 26.7% ± 2.19% of the 320 mg dose (4 × 80 mg capsules) when the endotracheal tube was used. With the shorter tracheostomy tube, the delivery dose increased to 35.6% ± 3.01% and 39.5% ± 2.04% of the 160 and 320 mg doses, respectively. The volume median diameters of the aerosols were in the respirable range with the largest value being 5.17 ± 0.87 μm.
Conclusions:
This delivery system has been shown to consistently deliver a high respirable dose of mannitol powder. Since this setup does not require disconnection of patients from the ventilator, it is safer for hypoxemic patients and easier to be adapted in a real clinical use.
Insights
A novel system delivers dry powder mannitol to mechanically ventilated patients, improving sputum clearance and reducing risks associated with ventilator disconnection. This method enhances patient safety and clinical applicability for respiratory infections.
Area of Science:
- Respiratory Medicine
- Biomedical Engineering
- Pharmacology
Background:
- Mechanically ventilated patients face high risks of pneumonia and hypoxemia due to poor sputum clearance.
- Dry powder mannitol is known to enhance sputum clearance.
- Existing administration methods pose risks due to ventilator disconnection.
Purpose of the Study:
- To develop and evaluate a novel system for administering dry powder mannitol to mechanically ventilated patients.
- To ensure mannitol administration without disconnecting the patient from the ventilator.
- To assess the delivered dose and particle size of aerosolized mannitol.
Main Methods:
- A three-way valve split the ventilator's inspiratory line, directing air through a dry powder inhaler (Osmohaler™) when needed.
- Mannitol powder was aerosolized during the inspiratory cycle.
- In vitro delivery dose and particle size distribution were measured using endotracheal and tracheostomy tubes at various airflow rates.
Main Results:
- The system delivered 24.6% (160mg dose) and 26.7% (320mg dose) of mannitol via an endotracheal tube.
- Delivery efficiency increased to 35.6% (160mg) and 39.5% (320mg) with a tracheostomy tube.
- Aerosol particle sizes were within the respirable range, with a maximum median diameter of 5.17 ± 0.87 μm.
Conclusions:
- The developed system effectively delivers a significant respirable dose of mannitol powder.
- The no-disconnection design enhances safety for hypoxemic patients.
- This system offers a practical and safer approach for clinical use in managing respiratory conditions in ventilated patients.
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