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

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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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