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Numerical Study of Spray Particle Deposition in a Human Nasal Cavity

Numerical Study of Spray Particle Deposition in a Human Nasal Cavity

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05/26/2014

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 Aerosol Science and Technology
, 40:1034–1045, 2006Copyright
c
American Association for Aerosol ResearchISSN: 0278-6826 print / 1521-7388 onlineDOI: 10.1080/02786820600924978
A Numerical Study of Spray Particle Deposition in a HumanNasal Cavity
K. Inthavong,
1
Z. F. Tian,
1
H. F. Li,
1
J. Y. Tu,
1
W. Yang,
2
C. L. Xue,
3
and C. G. Li
3
1
School of Aerospace, Mechanical and Manufacturing Engineering, RMIT University, Australia
2
 Division of Minerals, Commonwealth Scientific and Industrial Research Organization, Australia
3
School of Medical Sciences, RMIT University, Australia
Particledepositionalstudiesfromnasalspraysareimportantforefficient drug delivery. The main influences on deposition involvethe nasal cavity geometry and the nasal spray device of which itsparameters are controlled by the product design. It is known thatlarger particle sizes (
10
µ
m) at a flow rate of 333 ml/s impactin the anterior portion of the nose, leaving a significant portion of the nasal cavity unexposed to the drugs. Studies have found corre-lations for the spray cone angles and particle sizes with depositionefficiencies. This study extends these ideas to incorporate other pa-rameters such as the insertion angle of the nasal spray and theinjected particle velocity to observe its effect on deposition. A nu-merical method utilizing a particle tracking procedure found thatthe most important parameter was the particle’s Stokes numberwhich affected all other parameters on the deposition efficiency.
INTRODUCTION
Nasal drug delivery is a popular way to treat respiratory ail-ments such as congestion and allergies. It has become an alter-native to oral and injection routes of delivering systemic drugsfor a variety of diseases and its advantages have been well doc-umented (Hinchcliffe and Illum 1999; Djupesland et al. 2003).Information regarding particle deposition within the nasal cav-ity can be used for effective design of a nasal sprayer device todeliver drugs to specific targeted sites. Various studies adoptinghumansubjectsornasalcavityreplicashavefoundrelationshipsfor particle deposition efficiencies with nasal spray parameters,such as spray cone angle and the particle size distribution pro-duced(Chengetal.2001;Sumanetal.1999;Chengetal.1996).Howeverin-vivoandnasalcavityreplicamethodsused,limitthescope of studies due to their tendency to be intrusive, time con-suming and expensive in implementation. Numerical analysis
Received 23 May 2006; accepted 26 June 2006.The financial support provided by the Australian Research Council(project ID LP0347399) is gratefully acknowledged.Address correspondence to Professor Jiyuan Tu, School of Aerospace, Mechanical and Manufacturing Engineering, RMIT Uni-versity, PO Box 71, Bundoora Vic 3083, Australia. E-mail: jiyuan.tu@rmit.edu.au
allows a wider range of studies (e.g., repeatability and accuracyof a nasal spray injection released from the same location) thatis based on advancements in computational models employingComputational Fluid Dynamics (CFD) techniques (H¨orschleret al. 2003; Yu et al. 1998; Keyhani et al. 1995). The main ad-vantages include the graphical representation of results such aslocalparticledepositionsites,particleandairflowpath,velocitycontoursandvectorsatanylocation.HoweveronedisadvantageofCFDisthereliabilityofresults,whichisdependentonthecor-rect mathematical formulation for the process under simulation,i.e., the more realistic boundary conditions imposed along withgreaterdegreeofaccuracyinthenumericalalgorithmsofthesys-tem of equations, the more precise the solution will be. Further-more,thereisnosingleturbulencemodelthatcanreliablypredictall turbulent flows found in practical applications with sufficientaccuracy,thusmoreeffortsarestillrequiredtoimprovethisCFDaspect.Spray particle deposition is determined by several parame-ters: (1) gas phase flow field such as velocity and turbulenceeffects; (2) deposition mechanisms involving the interaction be-tween particles and its continuum; (3) particle material proper-ties and initial spray conditions such as particle density, size,and spray cone angle.Firstly, knowledge of the flow field allows the prediction of particle deposition which is determined by the complex geome-try of the nasal cavity. Kelly et al. (2000) presents detailed flowpatterns within a replica cast of a human nasal cavity. It wasfound that a small standing eddy was formed in the olfactory re-gions, low flow occurred in the turbinate regions and the highestvelocities were reached along the floor of the nasal cavity and atthe nasal valve where the cross-sectional area is smallest. Thisconfirmed with Keyhani et al.’s (1995) numerical simulationof airflow in the human nasal cavity. Furthermore, Kublik andVidgren (1998) point out that due to sudden changes in geome-try, turbulence production is enhanced, causing high depositionto occur at the nasal valve and at the atrium.Secondly, particle depositional studies also involve the inter-action of particles with its continuum. Lippman et al. (1980)discusses three main mechanisms for deposition of inhaled1034
 
SPRAY PARTICLE DEPOSITION IN HUMAN NASAL CAVITY
1035drug particles: inertial impaction, gravitational sedimentation,and Brownian diffusion. Particles in the sub-micron rangewill deposit by Brownian diffusion (Gonda and Gipps 1990),whilst inertial impaction is the dominant mechanism for par-ticles larger than 1
µ
m. Where the probability of inertialimpaction,
 I 
=
Qd 
2
 p
[1]is a function of the aerodynamic diameter and air stream ve-locity, (Kublik and Vidgren 1998). Further studies from Kellyetal.(2004)andEcketal.(2000)showhighdepositionefficien-cies (
>
95%) for inertial parameter values greater than 3
×
10
4
µ
m
2
cm
3
 /s.Finally, the nasal spray device initializes the drug deliveryprocess setting the particle’s initial conditions. Recent studieshave measured spray characteristics, such as particle size andspray cone angle (Suman et al. 2002; Dayal et al. 2004; Eck et al. 2000). A nasal spray produces drug particles in the rangeof5
µ
mupto200
µ
mwithameanof45–65
µ
mandsprayconeangles ranging from narrow sprays at 35
to wide sprays at 70
.Newman et al. (1998) found that an increase in spray cone anglefrom35
to60
showedareductioninsizeofthedepositionareaas less of the spray was able to penetrate the narrow nasal valve.Cheng et al. (2001) found that deposition in the anterior regionincreased with an increase in cone angles. In contrast, Sumanet al. (2002) found that there wasn’t a significant difference indepositionpatternswithrespecttosprayconeangles.Itisarguedthatthechangesinsprayangleisunlikelytoalterthedistributionof droplets in the nose due to the narrow passageway of thenasalvalve,comparedwiththesprayplumeswhicharetentimesgreater. Thus the emitted plumes never have the opportunity tofreelydevelopinthenasalcavityastheywouldinanunconfinedspace.The differences in arguments stem from the numerous vari-ations that exist in studying nasal spray deposition efficiencies(Tu et al. 2004). Moreover, the effects of the insertion angleof the spray device, the location of the insertion and the ini-tial particle velocity were not discussed. It is the aim of thisstudy to examine these parameters and the influence it has onthe deposition of particles in the nasal cavity by numericalanalysis.
GEOMETRY AND NUMERICAL METHODSNasal Cavity Geometry Construction
A nasal geometry was obtained through a computed tomog-raphy (CT) scan of the nose of a healthy 25 year old, healthynon-smoking Asian male (170 cm height, 75 kg mass). Theconstructed geometrical model of a human nasal cavity wascreated using the solid modelling tool GAMBIT. Slices of thethree-dimensional CT image were taken at different positionsfrom the entrance of the nasal cavity to just anterior of thelarynx. The image analysis data consisted of 
xyz
coordinates
FIG. 1. Nasal cavity models of different mesh resolutions, 82,000, 286,000,586,000 and 822,000 cells.
of airway perimeters for cross-sections spaced at intervals of 1 to 5 mm depending on the complexity of the anatomy. Acomputational mesh was generated enveloping the anatomi-cal geometry, which was used to simulate the airflow. Themesh generation step presented the most labor-intensive partof the simulation process because of the requirement of mesh-ing the intricate surface topology of the airway geometry. Adenser mesh distribution was concentrated near the surfaceboundaries in regions where relatively large velocity gradientsexist.A preliminary model was created with a mesh cell count of 82,000.Thiscoarsemeshunderwentenhancementtechniquestoaddressqualitycriteriasuchascellskewness,y
+
wallboundaryconditionsandcell-to-cellvolumechange.Threefurthermodelswere created, each retaining the same geometry but differing intheirmeshsizes(286,000cells,586,000cells,and822,000cells)forcomputationtocheckforgridindependencythroughconver-gence of results. Figure 1 shows the resolution of the originalcoarse mesh (82,000 cells) and compares it with the enhancedmodels. An additional frontal view (looking into subject’s face)ofacoronalsection,closetothebeginningoftheturbinateregionis included.It is known that the accuracy of results increase for finermesh, however at higher computational costs. A grid inde-pendence test, allows for the optimum mesh grid size to bedetermined. The Navier-Stokes equations for the gas phasewere solved at 20 L/min and a velocity profile near the con-stricting nasal valve area was undertaken for each model andcompared. Figure 2 shows the velocity profile converge at amesh resolution of 586,000 cells and a further increase to822,000 cells shows no further improvement. Therefore thenasal cavity model with 586,000 cells is used for furtheranalysis.
 
1036
K. INTHAVONG ET AL.FIG. 2. Velocity profiles of a coronal section near the nasal valve region forthe four different nasal cavity models. The profile is taken along the line shownon the coronal section.
Numerical Methods
AgenericCFDcommercialcode,FLUENT6.1.2,wasusedtopredict the flow field of the continuum gas phase under steady-state conditions by solving the full Navier-Stokes equations.These equations were discretized using the finite volume ap-proach. The QUICK scheme was used to approximate the mo-mentum equation while the pressure-velocity coupling was re-alized through the SIMPLE method. The presence of turbulentflowhasbeenconfirmedinthehumannasalcavitywheretheflowvelocitycanreachashighas22m/s(Tuetal.2004).Additionallyturbulent flow was assumed and the
-
ε
turbulence model wasused for flows around 200–300 ml/s (Keyhani et al. 1995; Yanet al. 2004). The
-
ε
models are the most commonly used turbu-lencemodel,basedontheassumptionofisotropicturbulenceanda single eddy viscosity for all three components of the velocityvector. This can cause inaccuracies for flows with high swirlingaction which makes the turbulence anisotropic. However forflows in the nasal cavity that exhibit low levels of swirl the
-
ε
approximation may be sufficient given the low computationalcosts compared with more sophisticated approaches such asLargeEddySimulationsandtheReynoldsStressModel.ThegasphaseReynolds-Averagedconservationequationsalongwiththeequationsfortheturbulentkineticenergyanditsdissipationratecan be cast in the general form:
 x 
 j
(
 A
i
φ
)
 x 
 j
∂φ
 x 
 j
=
[2]continuity equation (
φ
=
1)
 A
i
=
ρ
g
u
g j
,
=
0
,
=
0; [3]momentum equation (
φ
=
u
gi
)
 A
i
=
ρ
g
u
g j
,
=
ρ
g
ν
g
,
,
=
P
/∂
 x 
 j
; [4]turbulent kinetic energy equation (
φ
=
κ
g
)
 A
i
=
ρ
g
u
g j
,
=
ρ
g
ν
g
,
/σ 
,
=
P
ρ
g
ε
g
; [5]dissipation equation (
φ
=
ε
g
)
 A
i
=
ρ
g
u
g j
,
=
ρ
g
ν
g
,
/σ 
ε
;
=
1
ρ
g
2
2
ij
1
/
2
2
ρ
g
ε
2
g
κ
g
+√ 
νε
g
where
ij
=
12
u
gi
 x 
 j
+
u
g j
 x 
i
[6]The realizable
κ
-
ε
model proposed by Shih et al. (1995) wasintended to address deficiencies experienced in the standardand RNG
κ
-
ε
models. The term “realizable” means that themodel satisfies certain mathematical constraints on the normalstresses, consistent with the physics of turbulent flows. The de-velopment involved the formulation of a new eddy-viscosityformula involving the variable
µ
in the turbulent viscosityrelationship:
ν
g
,
t
=
C
µ
κ
2
g
g
and a new model for the
ε
-equation based on the dynamic equation of the mean-squarevorticity fluctuation. The variable constant
1
can be expressedas:
1
=
max
0
.
43
,ηη
+
5
and
η
=
κ
g
ε
g
2
2
ij
1
/
2
[7]The variable
µ
, no longer a constant, is computed from:
µ
=
1
 A
0
+
A
s
κ
g
U
ε
g
; U
 
2
ij
+
˜
2
ij
;˜
ij
=
ij
2
ε
ijk 
ω
;
ij
=
¯
ij
ε
ij
ω
[8]while the model constant
A
0
and
A
s
are determined by:
 A
0
=
4
.
04 ;
A
S
=√ 
6cos
ϕ
;
ϕ
=
13cos
1
(
√ 
6
);
=
ij
 j
ki
˜
3
;˜
=
 
2
ij
[9]Other constants in the turbulent transport equations are givento be
2
=
1.9,
σ 
κ
=
1.0, and
σ 
ε
=
1.2, respectively.
Lagrangian Particle Tracking Model
A Lagrangian particle tracking method is used to trace thedispersion of particles about the trajectory. The Lagrangianscheme is most popular in engineering applications for theprediction of particle flows because it can easily be combinedwith a stochastic Discrete Random Walk (DRW) scheme,albeit with high computational costs (Tu 2000). Trajectories

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