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CFD analysis of the aerosolization of carrier-based dry powder inhalerformulationsQi (Tony) Zhou, Zhenbo Tong, Patricia Tang, Runyu Yang, and Hak-Kim Chan Citation: AIP Conf. Proc. 1542, 1146 (2013); doi: 10.1063/1.4812139 View online: http://dx.doi.org/10.1063/1.4812139 View Table of Contents: http://proceedings.aip.org/dbt/dbt.jsp?KEY=APCPCS&Volume=1542&Issue=1 Published by the AIP Publishing LLC. Additional information on AIP Conf. Proc.Journal Homepage: http://proceedings.aip.org/ Journal Information: http://proceedings.aip.org/about/about_the_proceedings Top downloads: http://proceedings.aip.org/dbt/most_downloaded.jsp?KEY=APCPCS Information for Authors: http://proceedings.aip.org/authors/information_for_authors
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CF
1 A
Abstrthe aesize, dwere emouthmountanalysdifferethroat
KeywPACS
Aerosare amotherapeutPerformaincludingenvironmof inhalaerosoliz
The einlet sizethe de-adrug-onlyComputaused in field genmechanisagglomer
Previoof drugefficiencyintroducecalled cadrug partcarrier pparticles into the r
FD Anal
Qi (To
Advanced Dru2 School of Ma
ract. This studyerosolization of decreasing the mexamined. It w
hpiece. When tht of inhalable fisis indicated thence was show.
words: CFD, aerS: 47.55.-t, 47.1
INTR
sols generatedong the mosttic agents byance of DPI g formulatioment and patieler devices pzation of the Deffect of grid se and mouthpgglomeration y formulationational Fluid these series o
nerated in the sm of the efferation. ous studies mg-only systemy, large exed to a powdarrier-based Dticles to adheparticles. Upare liberated
respiratory tree
lysis of tPow
ony) Zhou
ug Delivery GMaterials Scien
y applied compf a carrier-basedmouthpiece len
was observed thhe inlet size wasine particles belhat the increase
wn in FPF when
rosolization, dry11.-j
RODUCTIO
d by dry powdt promising y inhalation depends on
on design, ents’ inhalatioplays a crit
DPI formulationstructure, mouiece geometryof mannitol
n has been iDynamics (Cof studies to device and th
fect of device
mainly focusedms. To imxcipient parder inhalation
DPI formulatioere to the surpon aerosoliz
from the care while the ca
the Aerwder Inh
u1, Zhenbo Ha
Group, Facultyce and Engine
putational fluid d dry powder inngth and increaat there was nos reduced to onlow 5μm in the e in FPF was dn the grid voida
y powder inhale
ON
der inhalers (Dforms to deto the lungs
n many varidevice selec
on [1]. The dical role onns. uthpiece lengty of Aerolizer powders froinvestigated [
CFD) analysissimulate the
hus to elucidatdesign on th
d on the dispemprove disperticles are n system. Theon enables therface of the czation, the rrier and deliv
arriers impact i
rosolizathaler F
Tong2, Paak-Kim Ch
y of Pharmacy,eering, Univer
dynamics (CFDnhaler (DPI). Tsing the mesh o significant in
ne third of the oraerosol, was im
due to increasiage was increas
er, device
DPIs) eliver s (1). iables ction,
design n the
th, air r® on om a [2-4]. s was
flowte the
he de-
ersion ersion often e so-e fine coarse
drug vered in the
thr
devbasper
gri3) of
FIGAe
tion of Cormula
atricia Tanhan1
, The Universirsity of New So
D) analysis to inThe inhaler devi
grid voidage. Tfluence on the riginal one, the
mproved signifiing air velocitysed, but more d
roat and are swIn this study,
vice design osed DPI systrformed.
Aerolizer deid mesh with 1/3 mouthpiethe original an
GURE 1. Derolizer devices.
Carrierations
ng1, Runyu
ity of Sydney, outh Wales, Sy
nvestigate the rice was modifieThe flow pattern
aerosol perform fine particle frcantly from 17.
y for the smalldrugs deposited
wallowed. , systemic inv
on the aerosoltems with aid
METHO
vice was moda higher viod
ece length. Fignd modified d
Diagrams of t.
r-based
u Yang2,
Sydney, Austrydney, Austral
role of device ded by reducing ns in the inhalemance with theraction (FPF), d.7% to 24.3%. Tler inlet. No sid in the mouthp
estigation of tl performanced of CFD an
ODS
dified to havedage; 2) 1/3 aigure 1 shows tdevices.
the original an
Dry
ralialia
design on the inlet
er device e reduced defined as The CFD ignificant piece and
the effect of e of carrier-nalysis was
e 1) a cross ir inlet size; the diagram
nd modified
Powders and Grains 2013AIP Conf. Proc. 1542, 1146-1149 (2013); doi: 10.1063/1.4812139
© 2013 AIP Publishing LLC 978-0-7354-1166-1/$30.00
1146
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The ina multi-sUK) wiForadile®
Limited, labeled dThe dispand relameasurememitted ddrug emduring thtotal loadof drug prelating teformoteperformaShimadzu
CompANSYS model wwere givtotal airflboundaryThree grcomputatvariablesresults wmesh sizethe rangecriteria to
Lagrapost proc(UDF) loparametenumber Lagranginumber ohave mutracked inhaler winfluencemay impa
R
Therebetween grid (p>0velocitymouthpieother hanfor the oinlet sizeattributed
n vitro aerosostage liquid ith a USP
® (Novartis North Ryde,
dose of 12 �gersion time w
ative humiditiments were cadose was calc
mitted from thhe aerosolisatid (FPF total) wparticles withto the total d
erol fumarateance liquid chu, Kyoto, Japaputational FluFluent 13 waas used for th
ven an area aflow rate. A vy conditions rid domains wtion. The diffes examined, were independe. The normale of 10-4 haveo ensure full cangian particlecessing operatoaded into ANers were set of steps and
ian particle of particles insuch effect on
each individuwall and ne
e. The wall waact on it.
RESULTS A
e was no signthe original, 1
0.05). There wdistribution
ece length devnd, the FPF tooriginal devicee was reduced d to the incr
ol performanceimpinger (Coinduction poPharmaceutic, Australia) ceformoterol f
was 4 s at 60 ies of 50 ± arried out forculated as thehe capsules aion. The fine pwas calculated
h the aerodynadrug load. The was assahromatographan).uid Dynamic
as performed. he airflow simaveraged velovelocity inlet a
were used inwere tested i
ference was lesuggesting thent of the chalized Reynoldsbeen applied aonvergence.e tracking wation with a use
NSYS Fluent. as 50000 f
d step lengthtracking was
serted into thethe impactionual particle
eglect the paas set to reflec
AND DISCU
nificant differ1/3 mouthpiec
was no apparenbetween the
vices, as showotal increased e to 24.3 ± 0to one-third (
reased air ve
e was evaluateopley, Nottingort (throat). als Australia
capsule contafumarate dihydL/min (20 ± 3 %). Trip
r each device. percentage o
and inhaler dparticle fractiod as the percenamic diameterhe drug conteayed using hy (Model LC
cs analysis uA Reynolds s
mulation. The ocity based onand pressure on all simulatin our prelimess than 5% fohat the comparacteristics os stress residuas the converg
as performed er defined funThe DPM tracfor the maxih factor of 5s performed,e inhaler wouln result as it impacting onarticle to pact any particle
USSIONS
rence in FPF ce length and nt difference original and
wn in Fig.2. Ofrom 17.7 ±
0.5% when th(p<0.05). Thiselocity inside
ed by gham, Each
a Pty ins a drate. 3 °C licate . The of the device on of ntage r < 5
ent of high
C-20,
using stress inletsn the outlet tions.
minary for all puted of theals in gence
as a nction cking imum 5. As , the ld not
only n the article s that
total cross in air
d 1/3 On the
0.5% he air s was e the
inhenhcar
haler device (hanced the rriers, therefor
FIGURE 2. C
(Fig.2). Such detachment ore, resulting in
CFD analysis of
increase in aof drug partn higher FPF t
f air velocity in
air velocity ticles from otal.
the inhalers.
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AlthoFPF totadevices, 3). More the cross grid cremouthpiepatterns and inhaerosoliz
ough there waal between ththeir depositidrugs depositgrid device b
eated more ece and throatcaused more
haler as wezation, thus, m
as no signifihe original anon patterns wted in mouthpecause increasswirling air
t (Fig. 4). Suc interactions ell as thromore drug de
FIGURE
cant differencnd the cross
were different piece and throasing the voida
flow patterh swirling air between par
oat walls depositions in
3. Drug depos
ce in grid
(Fig. at for
age of rn in flow
rticles during
these
twnotbelcarchamoparandstacar
ition patterns fr
o parts for thet cause signifilieve the detarrier surface amber and/or outhpiece andrticles escapedd induction po
ages 1 and 2rriers.
rom multi-stage
e cross grid dicant changes achment of the
mainly occthrough the g
d induction pd the depositiort of the orig2 instead, to
e liquid impinge
device. Howevin the FPF tote drug particlcurs inside tgrid prior to eort. Thereforeion from the ginal device dgether with
er.
ver, this did tal here. We es from the the inhaler entering the e, the drug mouthpiece
deposited on the lactose
1148
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FIGURE will travel
The mthe aeroCFD resdifferencmouthpieperformareduced. increasesgrid deviand throaThis studdevice haof carriertool in indevice.
4. Streamlinesl during the air f
CON
mouthpiece lensolization of
sults confirmece in the aece length wance was sho
These impros in air velociice had more at due to the dy demonstratas a significanr-based DPIs.
nvestigating th
s that are instantflow through in
NCLUSION
ngth had no siForadile fro
ed that there air flow pa
was reduced. own after th
ovements wereity inside the drug depositmore swirlin
tes that the dnt influence on. CFD is shohe air flow pa
taneously tangenhaler device an
NS
ignificant effeom Aerolizer.
was no obseatterns when
Improved aehe inlet size e attributed todevice. The
tion in mouthg air flow pa
design of Aeron the aerosolizwn to be a u
attern in the in
ent to the velocind throat.
ect on The erved
the erosol
was o the cross
hpiece attern. olizer zation useful nhaler
S.pfinCo
1.
2.
3.
4.
ty vector of the
ACK
The authorsp.A. for providnancially suppouncil (Grant D
N. Islam anPharmaceuticsM.S. Coates, Journal of PhaM.S. Coates, Journal of PhaM.S. CoatesChiou. Pha(2007).
e flow, show the
KNOWLED
s would like ding Aerolizeported by thDP110105161
REFEREN
nd E. Gladki. s. 360:1-11 (200H.K. Chan, D.
armaceutical SciD.F. Fletcher,
armaceutical Scis, H.K. Chanarmaceutical
e direction a par
DGEMENT
to thank PLer devices. Thehe Australian1).
NCES
International 08).F. Fletcher andiences. 95:1382H.K. Chan andiences. 93:2863
n, D.F. FletchResearch.
rticle element
T
LASTIAPE e study was n Research
Journal of
d J.A. Raper. 2-92 (2006). d J.A. Raper. 3-76 (2004). her and H.
24:1450-6
1149
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