Nebulized aerosol deposition in a realistic nasal cast model
during inhalation and exhalation
L. Vecellio(1,2), M. Francis (1), D. Le Pennec (1), G. Williams (3), E. Duclos (4), P. Diot (1)
(1) CEPR/INSERM U1100/EA 6305, Faculté de Médecine, Université François Rabelais, Tours, France. (2) DTF-Aerodrug, Faculté de Médecine, Université François Rabelais, Tours, France,
(3) Aptar Pharma, Le Vaudreuil, France, (4) SOS STAT Doussard, France
.
Introduction
Aerosol drug delivery is one of the most powerful tools used to treat nasal cavity inflammations and infections. Drug delivery through the nose presents the advantage of
targeting the zones of interest and avoiding the first-pass metabolism.
The aim of this work is to study the influence of the micrometric particle size (1 to 10µm in terms of Mass Median Aerodynamic Diameter(MMAD)) and the air flow rate
during inhalation and exhalation process on nasal aerosol deposition. In order to carry out this cartography, a nasal cast model was built from epoxy plastic based on
computed tomography. The nasal cast can be dismantled in 4 parts allowing the measurement the aerosol deposited into the different regions (nose, nasal valve, turbinate,
maxillary, ethmoidal and frontal sinuses, sphenoid and nasopharynx).
Material: Nasal cast model
Experimental setup
-During the inhalation process, the nebulizer was connected to one nostril,
while the second nostril was closed.
-During the exhalation process, a compressed air bottle connected to a
humidifier and to a heater was used to achieve the exhalation flow rate via a
T-piece connected to the nasopharynx and the nebulizer.
-Particle size penetrating into the maxillary sinuses was measured using a
low flow cascade impactor.
Aerosol delivery during inhalation process
Aerosol delivery during exhalation process
The nasal cast model was built from epoxy plastic based on CT-scans
Duration: 5 min
Flow rates: 2/ 7 /15 L/min.
Volume Mean Diameter :
2/ 4.5 /9.5 µm.
Flow rates : 2 /15 / 90 L/min.
Volume Mean Diameter : 1.1/ 4.7/9.8 µm.
e
Tracer : fluorescein solution
The deposited fluorescein was assayed by UV spectrophotometry
Results
A multiple linear regression analysis was used in order to evaluate the correlation between deposited mass and the VMD and the air flow rate
The deposited mass on each zone was normalized to the total deposited mass in the model and in the filter.
16%
14%
12%
10%
8%
6%
4%
2%
0%
0
5
10
15
air flow rate (l/min))
20
35%
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
7l/min
VMD (µm)
2
4,5 9,5
2
4,5 9,5
2 L/min
30%
deposited mass (%)
deposited mass (%)
deposited mass (%)
VMD = 4,5 µm
Nose + nasal valve
Turbinates
Nasopharynx
2
4,5 9,5
15 L/min
90 L/min
25%
20%
15%
10%
5%
0%
Nose + nasal valve Turbinates Nasopharynx
VDM (µm)
1,1
4,7
9,8
Nose +nasal valve
1,1
4,7
Turbinates
9,8
1,1
4,7
9,8
Nasopharynx
Deposited mass during inhalation: Nose+ nasal valve: 0.4 to 30 %. Turbinates: 0.2 to Deposited mass during exhalation : Nose+ nasal valve: 0.5 to 16.2 %. Turbinates: 0.3
to 24.1 %. Nasopharynx: 0.1 to 27%, Filter: 97 to 23%
11.5 %. Nasopharynx: 1.5 to 2%, Filter: 97 to 56%
Statistical analyses (of all the results) : correlation between the mdep in the nose
and the nasal valve and the VMD (R2>0.82). For the turbinates a correlation was
found between mdep and the 2 tested parameters the VMD and the flow rate
(R2=0.82). Same conclusion for the nasopharynx (R2>0.76) and the filter (R2> 0.96).
Statistical analyses : correlation between the mdep in the nose and the nasal valve
with the flow rate and the VMD (R2>0.85). Same conclusion for the turbinates
(R2=0.91), the nasopharynx (R2=0.97) and the filter (R2 > 0.98).
The particle size penetrating into the maxillary sinuses of the nasal cast model had a constant 2µm MMAD size, whatever the flow rate.
CONCLUSIONS
Aerosol deposition in the nose, the nasal valve, the turbinates, the nasopharynx and the filter is correlated to the particle size or/and air flow rates .
Aerosol deposition in the ethmoidal, maxillary, sphenoidal and frontal sinuses could not be predicted by using flow rate and particle size.