Powder Technology 240 (2013) 1924

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Powder Technology
journal homepage: www.elsevier.com/locate/powtec

CFD-DEM investigation of the dispersion mechanisms in commercial

dry powder inhalers
Z.B. Tong a, B. Zheng a, R.Y. Yang a,, A.B. Yu a, H.K. Chan b
a
Laboratory for Simulation and Modelling of Particulate Systems, School of Materials Science and Engineering, University of New South Wales, Sydney, NSW 2052, Australia
b
Faculty of Pharmacy, University of Sydney, NSW 2006, Australia

a r t i c l e i n f o a b s t r a c t

Available online 6 July 2012 This paper elucidates the important role of numerical technique in investigating powder dispersion mecha-
nisms in pharmaceutical dry powder inhalers, using the commercial Aerolizer as a model inhaler device.
Keywords: A coupled computational uid dynamics (CFD) and discrete element method (DEM) technique was adopted
Computational uid dynamics to simulate uid ow and particles, respectively. The shear stress of turbulent ow had no visible effect on
Discrete element method powder dispersion while the agglomerateagglomerate interactions occurred only when the agglomerates
Aerosol
were ejected from the capsule. Multiple major impactions occurred between the agglomerates and the cham-
Dispersion particulate processes
Pharmaceuticals
ber wall, which fragmented the agglomerates into large pieces without generating many ne particles. The
subsequent impactions between the fragments with the grid were identied as the key factor for the dramatic
increase in FPF (i.e. amount of ne particles below 5 m in the aerosol). The inhaler was more efcient with
increasing air ow rate in terms of the FPF, but its performance decreased at a higher ow of 130 Lmin 1
due to much larger depositions (i.e. increased device retention). This work has demonstrated the capability
of CFD-DEM modeling to study various dispersion mechanisms and their relative importance, which provides
a rational basis for future improvement of inhaler devices.
2012 Elsevier B.V. All rights reserved.

1. Introduction
Inhalation aerosols offer the distinct advantage of rapid and con-
venient delivery of bioactive substances to the site of action [13].
Recently signicant research effort has been directed towards the de-
velopment of innovative technologies for the generation and delivery
of dry powder aerosols for inhalation [4]. Compared with other inha-
lation technologies, dry powder aerosols require no propellant, have
superior chemical stability, better bacterial growth resistance and are
easy to use [5]. However, present pharmaceutical dry powder inhalers
(DPIs) are extremely inefcient (only 1030% of the stated dose reaches
the lungs) and have large variability of dosing [4,6]. Lack of understand-
ing of dispersion mechanisms is a major obstacle to further improve
inhaler performance.
Powder dispersion in inhalers is a highly dynamic process affected
by various interactions among powders, air ow and inhalation devices
[1,7,8]. The knowledge of such information is useful to understand the
underlying mechanisms of dispersion but is difcult to be obtained
from experiments [911]. As such major efforts have been made recently
to numerically model the process [1214]. By using computational uid
dynamics (CFD) method, Coates et al. [1517] showed the signicant
effects on the DPI performance by small changes in the device design
Corresponding author.
E-mail address: r.yang@unsw.edu.au (R.Y. Yang).
(grid size, mouthpiece geometry, inlet air dimension, and air-ow rate).
Matida et al. [18] shows the role of computational uid dynamics on
the design optimization of inhaler. Their model, however, could not
explicitly incorporate particle material properties, such as interparticle
cohesion and their effects on the particle interaction with shear ow
and devices. On the other hand, we recently developed a numerical
model based on the combined CFD and discrete element method (DEM)
approach. With this model, we have simulated the de-agglomeration of
particles under various conditions [1921]. The simulation results were
comparable to measured data, mainly in terms of ne particle fraction
and powder deposition. The microdynamic analysis at particle scale was
performed based on the simulation results and the dominant dispersion
mechanisms for each condition were identied. Furthermore, an index
based on the energy ratio was proposed to characterise the dispersion
efciency.
While the model provides a technological platform for modelling
powder dispersion in DPIs, previous simulations were carried out under
relatively simple and ow conditions which were specically designed
to investigate one dispersion mechanism at a time (e.g. powder-wall me-
chanical impactions). In commercial devices, the breakage mechanisms
are highly complex and the interplay of the interactions among the pow-
der, air ow and device affect collectively the dispersion process. For
example, in the commercial Aerolizer inhaler which was investigated
by Coates et al. [17], powders are ejected from the spinning capsule and
dispersed due to the shear ow and mechanical impaction with the
device, including a grid at the beginning of the barrel. Therefore, accurate

0032-5910/$ see front matter 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.powtec.2012.07.012
20 Z.B. Tong et al. / Powder Technology 240 (2013) 1924

simulation of the dispersion and better understanding of dispersion
mechanisms relevant to inhalers and powder properties are critical to
rening the device.
The present work applies the CFD-DEM approach to powder dis-
persion in a more complicated condition involving various dispersion
mechanisms. A commercial Aerolizer inhaler model is chosen so that
the present results can be compared with experimentally measured
data and previous CFD results [1517,22]. Specically, the effects of
spinning capsule and inhaler grid will be investigated.
2. Model development and simulation condition
2.1. CFD-DEM model
The description of CFD-DEM model has been detailed in the previ-
ous papers [23] and is only summarised here. By treating the disper-
sion process as a particleuid ow, the discrete particles and the
continuous air ow are modelled by DEM and CFD, respectively. In
DEM model, the motions of a particle (of mass mi and radius Ri) are
governed by Newton's second law of motion [24]:
X i  k 
dv
mi i f cn;ij f dn;ij f ct;ij f dt;ij f v;ij f pf ;i mi g
dt
j1
  
i   
di X
k
 ^
Ii Ri  f ct;ij f dt;ij r f cn;ij 
dt j1
i under an assumed centripetal force to move particles toward the cen-
where mi, Ii, vi , and i are, respectively, the mass, moment of inertia,
translational and rotational velocities of particle i. R i is the vector from
the centre of particle i to a contact point. kiis the number of particles
contacting with particle i. r is the rolling friction coefcient. ^i
i =ji j. The forces involved are the gravitational force, mi g, inter-
particle forces between particles i and j, which include the normal
and tangential contact forces f cn;ij and f ct;ij , the viscous damping forces
f dn;ij and f dt;ij , the van der Waals force f v;ij , and the particleuid inter-
action force, f pf ;i .
The motion of uid in CFD model is governed by the Navier
Stokes equations, given by [2527]
tensor, respectively. The volumetric uidparticles interaction force
Ffp is dened as the summation of the particleuid interaction fpf
over all the particles in a CFD cell. Detailed descriptions of the forces
can be found from [28,29]. Commercial software Fluent was used for
the CFD simulations and the Dynamic Mesh Model was adopted to
model the spinning capsule.
The CFD-DEM coupling is achieved by combining an in-house built
DEM with Fluent through its User Dened Functions (UDFs). A two-
way coupling method was adopted so the information from DEM
and CFD was exchanged at each step. At each time step, based on
uid ow eld, DEM calculates particle-related information based
on uid ow eld, such as the positions and velocities of individual
particles, to determine porosity and volumetric particleuid interac-
tion force in the individual computational cells. CFD then uses these
data to determine the air ow eld which then yields the particle
uid interaction forces acting on individual particles. Incorporation
of the resulting forces into DEM produces information about the
motion of individual particles for the next time step, and the process
continues [28].
2.2. Simulation conditions
1
Fig. 1a shows the inhaler device in the present study. The inhaler
consists of a chamber with two inlets, a barrel and a grid in between.
A capsule is inside the chamber to store agglomerated powders. In the
simulation, the agglomerates were formed with mannitol powders
2
tre. After all the particles reached their stable positions when the par-
ticle kinetic energy was dissipated, the centripetal force was removed
and the agglomerates were relaxed to remove the residual effect of
the centripetal force [19]. The mannitol powders had a size distribu-
tion as shown in Fig. 1b with the mass mean diameter of 3.27 m.
All formed agglomerate had a same diameter of 51 m with porosity
of 0.5 and the theoretical tensile strength of 1.21 kPa from the
Rumpf's model [19,30], given by
0 1
1 X X
N zi
1
t ii r@ n f A 5
3 3V i i j1 ij v;ij

where V is the volume of the agglomerate, N the total number of par-

u 0 3
t ticles, ri the particle radius, zi the coordination number and nij the unit
  vector connecting the centres of particles i and j, fv,ij van der Waals

f u     force at the contact points of particles i and j. All the necessary infor-
u
f u  PFfp f g u0 u0
t mation in Eq. (5) is readily available from the present simulations.
4 Therefore, the tensile strengths of agglomerates composed of differ-
ent sized particles can be determined. The particle properties have
 , u, f, P and are porosity, uid mean velocity, turbulent
where , u signicant effects on dispersion, as discussed in our previous paper
velocity uctuation, uid density, pressure and uid viscous stress [23]. In the current work, the particle properties and tensile strength

a b
0.3
density function (mass)

Air Inlet

Grid
Probability

0.2
Outlet

Air Inlet
Capsule 0.1

Barrel

0.0
0 1 2 3 4 5 6 7 8 9
Diameter (m)

Fig. 1. (a) Schematic view of the inhaler; and (b) size distribution of powders forming the agglomerate. The inset shows the formed agglomerate (colours represent particle diameters).
 Z.B. Tong et al. / Powder Technology 240 (2013) 1924 21

Table 1
50 Values of the key parameters used in the simulations.
0.7

Depositon % (by mass)

Parameter Value
40
Number of agglomerates, Nag 8
Number of particles in an agglomerate, np 3000
FPFloaded

0.6
Particle density, 1490 kg m3
30
Particle Young's modulus, Y 1 108 N m2
Poisson's ratio, 0.29
Sliding friction coefcient, 0.3
0.5 20
Hamaker constant, Ap 1.2 1019 J
Hamaker constant, Aw 6.5 1020 J
10 Air ow velocity, v 1050 m s1
Air ow rate, Q 27.6138 l min1
0.4 Capsule rotational speed, 37204968 rpm
0 2 4 6 8 10 12 14 16 18 20 22
Number of agglomerate

Fig. 2. Variations of FPFloaded and deposition percentage with number of agglomerates.
were selected to match those used in the experiments [31] so the
results can be compared. The simulation conditions were similar to
those in the experimental work [15]. A velocity inlet and pressure
outlet boundary conditions were used in all simulations. The penetra-
tion of agglomerates through the capsule was not simulated. Instead
at the beginning of the dispersion process, the agglomerates were
ejected from the two sides of the capsule into the air stream at pre-
scribed intervals and velocities which calculated from the spin speed
of the capsule. The agglomerates were impacted with each other and
device wall and, as a result of the interactions among the agglomerates
and with ow and device, were broken into small fragments which
were then discharged from the outlet. Different ow velocities from 10
to 50 m/s (equivalent to ow rates of 27.6 to 138 L/min) were used,
which are the typical values used in physical experiments [32,33] and
clinical testing [34]. It has been demonstrated [22] that the spin speed
of the capsule (rpm) varies linearly with ow rate, Q (L/min), given
by = 45Q. This relationship was used in the present study to deter-
mine the capsule speeds under different ow conditions.
Sensitivity tests were also carried out to ensure that the results
were independent of the computational mesh and the number of ag-
glomerates. To obtain mesh-independent results, three simulations
were run in which the characteristics of the mesh applied to the
geometry were varied signicantly. The results exhibited little differ-
ences on the three computational meshes, indicating the mesh inde-
pendence. Therefore, the following mesh sizes were adopted for all
simulations: 0.2 mm for the base and mouthpiece and 0.15 mm in
the region of the grid. The mesh sizes are comparable to the size of ag-
glomerates (0.05 mm) but much larger than the primary particles
(mean size 3.27 m). Similarly, simulations were run in which the
agglomerate number was varied from 2 to 20. It was observed from
Fig. 2 that the ne particle fraction (FPFloaded) initially increases
with the number of agglomerates, and then saturated with further
increase in the number of agglomerates. Therefore the dispersion of
8 agglomerates with total of 24,000 particles was selected in the fol-
lowing discussion. The values of some key parameters used in the
simulations are listed in Table. 1.
3. Results and discussion
3.1. Dynamics of air and powder ows
Fig. 3 shows the air ow at different times with the ow velocity
v = 30 m/s. The normalised time , dened as the ratio of time against
the device empty time, is used. The device empty time is the average
time of particles staying in the device before being discharged from
the outlet. It is observed from the side view in Fig. 3a that the ow
has the highest velocity near the grid and the lowest one at the centre
of the barrel. Compared with our previous work on a cyclonic device
[23] which has the same geometry and size but without capsule and
grid, the grid converts the tangential air ow entering the device
into a predominantly axial air ow exiting from the barrel, which
was also observed by Coates et al. [17] using CFD modelling. The top
view shows that, when the capsule is parallel to the inlets, large
velocity occurs just outside the inlets. When the capsule rotates to
the position perpendicular to the inlets, the ow velocity, however,
become much smaller.
Fig. 3b shows the spatial distribution of the integral scale strain
rate (ISSR). ISSR is a measure of the velocity gradient across the inte-
gral scale eddies (the most energetic occurring in a turbulence ow)
[35], given by
ui
i 6
l k
where ui is the integral velocity scale, l the integral length scale,
the rate of turbulent energy dissipation and k the rate of turbulence

Fig. 3. Side and top views of (a) velocity elds; and (b) ISSR elds at different times of = 0.3 and 0.5. v = 30 m/s.
22 Z.B. Tong et al. / Powder Technology 240 (2013) 1924

kinetic energy. ISSR has been demonstrated to be more relevant to a

agglomerate dispersion [22] as turbulent ow consisting of eddies 100

Cumulative % Undersize (by mass)

that exhibit large ISSR will exert large aerodynamic forces on particles
and hence will be more effective in breaking up agglomerates. In the 80
simulation, the points in a CFD cell have different values of shear
stress by linear interpolation of the values of in cell nodes. Therefore,
60
the effect of turbulent shear stress can be captured with the current
method. 10 m/s
30
It can be seen that ISSR has maximum values near the spinning 40
40
capsule and grid. While the largest shear stress under the current 50
condition is 2.7 kPa which is larger than the agglomerate tensile 20 Original
strength of 1.21 kPa, the region is very small and always near the
capsule surface. The majority of ow eld is covered with the shear
stress less than the strength of the agglomerate. Therefore, we did 0
0 2 4 6 8 10 12 14
not observe the breakage of agglomerate due to the turbulent ow. Diameter (m)
As mentioned above, this study focus on the dispersion of agglomer-
ates formed with the mannitol powders. For these agglomerates, the
inter-particle cohesion is far larger than the shear stress of the current
b
ow. However, if agglomerates have a looser structure or different 0.7 80
powders (e.g. carrier based formulation) are used, the turbulence of 70
ow may affect the dispersion efciency. 0.6

Depositon % (by mass)

60
It is observed from Fig. 3 that the spinning capsule does affect the
0.5
ow pattern inside chamber mainly from two aspects: First, the posi-

FPFloaded
50
tion of capsule affects the local ow pattern in the adjacent to the 0.4
40
capsule which causes different powder dispersion performance. Sec-
ond, the average ow properties in the chamber are also affected. 0.3 30
For example, the volume-average velocity and ISSR in the chamber
0.2 20
increase about 6% and 10%, respectively. As the change in ow pattern
affect powder dispersion, the inclusion of the spinning capsule in the 10
0.1
model provides a more accurate description of the dispersion process. 0
Fig. 4 shows the spatial distributions of particle velocity at the dif- 10 20 30 40 50
ferent times. It is clearly observed that the after multiple impactions Airflow velocity (m/s)
the agglomerates break into small fragments, some of which follow
the airow to reach the region of grid and others deposit inside the Fig. 5. (a) Size distributions of the fragments emitted from the outlet; and (b) FPFloaded
and deposition percentage with different airow rates. The line in (a) is the size den-
chamber and base. Comparing with the cyclonic model in our previ-
ing FPF.
ous study [23], the agglomerates stay longer in the chamber and
have multiple impactions with the wall. So the dispersion process is
more complicated than the cyclonic model. Other ow rates have 50 m/s is even smaller than that of particles in the original agglomerate,
similar distributions and are therefore not shown here. indicating some large particles that are retained inside the inhaler.
Fig. 5(b) shows the ne particle fraction and powder deposition as
3.2. Dispersion performance and mechanisms a function of ow rate. FPFloaded is the mass fraction of particles small-
er than 5 m in the emitted powders against the total mass loaded
Fig. 5 shows the dispersion performance of the inhaler under differ- into the inhaler. Dispersion is more efcient with increasing ow
ent ow rates. For the low ow velocity of 10 m/s, the fragments rate with the over ve folds increase in FPFloaded from 10 m/s to
from the outlet have relatively larger sizes with the median size D50 of 40 m/s. However, FPFloaded decreases sharply for v = 50 m/s, which
4.16 m. With increasing velocity, the distribution shift to smaller size, is mainly due the sudden increase of powder deposition (from 20%
giving better dispersion performance. The distribution of powders at at 40 m/s to 80% at 50 m/s). So the excessively high ow rate in fact

m/s

Fig. 4. Spatial distributions of particle velocity at = 0.3 and 0.5. v = 30 m/s.

 Z.B. Tong et al. / Powder Technology 240 (2013) 1924 23

20 a that the grid may not be that important. The seemingly contradictory
Vxz
10
8 ow and dispersion region. In dispersion, the grid acts as not only an
6 impaction surface but also a ow straightener to convert the air
Vy 4 b
2 ow from the tangential direction into an axial ow along the mouth-
0
Fpw
0.1 c mouthpiece wall. With an open grid, the ow will remain as tangen-
0.01
Fpp 0.1 d an impaction surface for powder deagglomeration, it serves to change
0.01
30
d50
15 e 4. Conclusions
0
FPF
0.6 f The powder dispersion in an inhaler was simulated by a coupled
0.3
0.01 0.02 0.04 0.060.080.1 0.2 0.4 0.6 0.8 1
Normalized time ()
Fig. 6. Time evolutions of the dynamic properties of agglomerate: (a) particle mean
velocity in the horizontal direction; (b) particle mean velocity in the vertical direction
(m/s); (c) total contact force between agglomerates and wall (mN); d) total contact
force between agglomerate and agglomerate (mN); and (e) d50 (m); (f) ne particle
fraction. v = 30 m/s.
reduces the dispersion efciency. Note the results are powder specif-
ic. If different powders other than mannitol are used, the results can
be different. The device shows high sensitivity to the change of ow
rate which may not be benecial to the usage of the device.
To examine which mechanism is more dominant in the process,
temporal variations of key parameters, such as the average velocities
of the particles in the horizontal and vertical directions, particle
particle and particlewall impaction forces and FPF, are plotted in
Fig. 6. Fig. 6(a) and (b) shows that particles are initially accelerated
by air ow but decelerate at = 0.018 when the rst major mechan-
ical impaction occurs. When the rst agglomerate impacts on the
wall (Fig. 6(c)) and subsequently with other agglomerates behind it
(Fig. 6(d)), four peaks can be clearly observed in the two gures,
representing the impaction forces on four agglomerates. As the rst
impaction is completed, the agglomerates are broken into many small
fragments, as reected from the decrease of d50 size in Fig. 6(e), however
only a small increase in FPF is observed at the same time (Fig. 6(f)). After
the rst impaction, the mechanical forces for particlewall and particle
particle diminish while the particleuid interaction results the increase
in particle velocity again. The second and third major impactions with
the device wall occur at =0.1 and 0.2, respectively (Fig. 6(c)). On
the other hand, the impactions among the fragments are much smaller
(Fig. 6(d)) and the fragments are lumped together again (Fig. 6(e))
due to these impactions. Again there is also no obvious increase in FPF.
Only from =0.3 can many small spikes be observed in Fig. 6(c). This
is because the fragments have moved to the grid region and the spikes
are the results and frequent collisions between the fragments and grid.
In the mean time, FPF has a dramatic increase.
Therefore, it can be concluded that the dispersion is mainly affect-
ed by particlewall impaction. The agglomerateagglomerate impac-
tions are only important at the very early stage while agglomerate-
uid interactions have almost no effect on agglomerate breakage.
Fig. 6 also indicates that the particlewall impactions inside the
chamber cause major damage to the agglomerates which are broken
into a few large fragments. Further impactions between the frag-
ments and the grid actually result the generation of large amount of
ne aerosol particles. It is interesting to compare the present results
with those by Coates et al. [17]. The current results clearly show the
grid plays an important role in ne powder generation, while the
study by Coates et al. [17] showed the open grid structure (just a
cross) produced similar FPF compared with the full grid, implying
ndings can actually be explained by a close examination of the uid
piece, which minimises the impaction between the powder and the
tial (or spiral) in the mouthpiece, causing powder-wall impaction to
facilitate deagglomeration. Therefore, a grid provides more than just
ow direction which in turn affects impaction and the subsequent
deagglomeration.
CFD-DEM model. The effect of spinning capsule was included by
using dynamic mesh technique. The performance of the inhaler under
different ow rates was investigated. Based on the microdynamic infor-
mation of particles, the dominant mechanisms were identied. It was
concluded that:
The dominant mechanism for this device is agglomerate-device im-
paction. The turbulent ow was not strong enough to break the ag-
glomerate and the agglomerateagglomerate impactions occurred
only at the very early stage when the agglomerates were spun out
from the capsule.
There were multiple strong impactions between the agglomerate
with the base, which caused the agglomerates broken into several
pieces. The impactions with the grid further broke the agglomerates
causing signicant increase in ne powders.
Inhaler performance was sensitive to the ow condition. Larger
ow rate reduced the size of fragments coming out the inhaler but
also increased the amount of powder deposition. So exceedingly
high ow rate may reduce the performance of the inhaler.
The authors want to emphasise that the above ndings are only
applicable to the current system in which loose agglomerates of ne
powders were dispersed. For other devices and powders (e.g. carrier
based formulation), the dispersion mechanisms may differ. Neverthe-
less, the current study elucidates the important role of numerical
technique in investigating powder dispersion mechanisms in phar-
maceutical dry powder inhalers.
Acknowledgments
Authors are grateful to the Australia Research Council (ARC) for
the nancial support.
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