1. In vitro comparison of two nasal delivery devices to administer dry powders
Rahul Kumar Verma1, Hooman Yari and Lucila Garcia-Contreras1 
College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City, OK, USA
RESULTS
INTRODUCTION
In general, %ED increased when the powder density decreased (table 1).
%ED from the SNBL device was consistently higher than from the Aptar device for all three test powders (table 1).
The variability in the %ED from the Aptar device was 5-fold larger that from the SNBL device for trehalose microparticles: the variability in the %ED from the Aptar device was 11.63% whereas for the SNBL device was 2.21%.
To achieve a successful therapeutic outcome using the nasal route, besides an optimal formulation, a robust, reliable and reproducible delivery device is required
Differences in emitted size and dose uniformity of therapeutic powders delivered by different nasal devices may result in variable clinical outcomes.
The multiple-use Fit-lizer™ (SNBL Ltd., Kagoshima, Japan) is a capsule-based nasal powder device. When inserted into the chamber of the device, the ends the capsule are cut off by sharp blades. To aerosolize the powder, a rubber bulb is compressed to produce air that passes through one-way valve (1).
The UDS powder nasal device (Aptar Pharma, Radolfzell, Germany) has a plunger that when pressed, pierces the membrane of a compartment containing the powder, thus creating a positive pressure that ruptures a membrane to emit a plume of aerosolized powder (2).
The differences in the mechanisms of aerosol generation of these devices suggest that they would also have differences in the emitted dose and emitted particle size.
The performance of these two nasal devices was evaluated in terms of reproducibility, accuracy and robustness to assess their suitability for in vivo studies.
Figure-1: UDS nasal device (Aptar Pharma):
(A) filling and assembling (B) UDS device with animal dosing tip
Table-1 : %ED of test powders from the Aptar and SNBL devices
The SNBL multiple-use Fit-lizer™ was loaded with a #2 capsule containing an accurately weighed (15 mg) amount of test powder for aerosolization (Steps 1-3, figure-2).
Test powder
Mean bulk density (g/ml)
Average % Emitted dose
Aptar
SNBL
Trehalose MP
0.050.01
90.56 ± 11.63
96.11 ± 2.21
Blend of trehalose MP and lactose
0.0980.01
88.34 ± 7.82
92.22 ± 5.78
Lactose
0.270.17
85.56 ± 9.34
86.89 ± 7.53
In general the emitted particle size from both devices was larger than their corresponding primary particle size, indicating that some aggregation of particles occurs upon aerosolization and passage through the nozzle of the device.
Notably, the size increase from primary particles was larger for particles emitted from the Aptar device (more than two-fold, Table 2) than from the SNBL device.
Figure-2- Multiple-use Fit-lizer™ Nasal device (SNBL, Ltd.)
Filling and assembling
Device with animal dosing tip
Table-2 : Comparison of the particle size distribution of aerosolized test powders emitted from the Aptar and SNBL devices
Test powder
Mean primary particle size (µm)
Mean volume diameter (dv50, µm)
Fold increase in size
Aptar
SNBL
Trehalose MP
14.570.06
33.79 ± 1.49
26.97 ± 1.41
2.31
1.83
Blend of trehalose MP and lactose
13.820.24
36.86 ± 2.07
24.79 ± 2.59
2.67
1.79
Lactose
15.30.34
30.99 ± 1.50
27.05 ± 1.09
2.03
1.76
METHODS
Emitted dose (%ED)
The Aptar device was loaded with the test powder and the nozzle was tightly coupled to the lid of a small glass vial. Powders were aerosolized by pressing the pump of the device, which was positioned at 60 (the position of the device while dosing the rabbits) on a wooden ramp stand. The amount of powder collected in the bottle was determined by subtracting the weight of the empty vial from the weight of the vial after aerosolization.
The SNBL device was loaded with a capsule filled with each test powder and the nozzle was tightly coupled to a pre-weighed polythene trap bag provided by SNBL. The test powder was aerosolized by squeezing once the pump of the SNBL device (positioned at 60)  and the %ED was determined by subtracting the weight of the empty bag from the weight of the bag and powder after the actuation.
Emitted Particle Size
The volume median diameter of the particles in the aerosol plume emitted from the two devices using the three test powders was measured by laser diffraction using the HELOS system with the RODOS dry dispersing unit (Sympatec, Germany). Each device was actuated so that the mid-region of the aerosol plume was read by the laser beam.
TEST POWDERS
Three powders of different densities were prepared for in vitro testing of the devices:
Micronized lactose powder
Trehalose microparticles powder
A (1:1) blend of lactose powder and trehalose microparticles
Individual test powders were sieved through a # 400 USP sieve (opening = 38 µm). The bulk density of powders was measured in a graduated cylinder.
DOSE LOADING
The container of the Aptar device was filled with an accurately weighed amount (3 mg) of each test powder (figure-1A); the container was closed with an insert, assembled within the nozzle and the nozzle was turned clockwise in order to lock the device.
CONCLUSIONS
The SNBL device appears to be more suitable for in vivo studies based on:
more reproducible and higher %ED; (b) the emitted particle size, and
(c) easiness to assemble, fill and actuate .
REFERENCES
Djupesland, PG: Nasal drug delivery devices: Characteristics and performance in a clinical perspective-a review, Drug Deliv Transl Res 2013, 3:
Haruta, S: How nasal delivery can meet the changing needs of patients and the drug development industry. ONdrugDelivery 2012, 37: 4-6.