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µ Pulmonary Drug
Delivery

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quizlet.com/551071051/aerosol-drug-therapy-
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ards/

1
Learning Objectives

At the end of the lecture you will be able to

• Describe the advantages of pulmonary drug delivery systems
• Describe the factors in>uencing the pulmonary drug delivery
• Explain the current technologies for pulmonary drug delivery
• List the applicaIons of pulmonary drug delivery

2
Introduction

• Pulmonary drug delivery system deals with the administration of

the therapeutic agents directly to the lungs via nasal or
oral route.
• Valuable tool in the local therapy of pulmonary diseases
such as asthma or Chronic Obstructive Pulmonary Disease
(COPD).
in and nit
stirwneearany
water innate

• Delivering locally acIng drugs (eg. anI-asthmaIc) directly to their

site of acIon, reduces the dose and systemic side eOects.
• Delivering systemically acIve drugs.
• e.g. insulin degradaIon by proteases, volaIle anaestheIcs (halothane),
ergotamine tartarate (migraine)

is as an ax on a wwai g

3
 nreon a
oa
aaim

Why Pulmonary drug delivery?

is on a x seumo asi je
• The lungs provide a promising portal for noninvasive delivery of drugs
to the blood and lymphaIc circulaIon.
• This facilitates absorpIon of drugs with slow or incomplete oral
bioavailability.

• The respiratory tract deal with exposure to 10,000 L of air (by

inhalaIon).

e aw
is
• The lung provides an enormous surface area through which molecules
can be absorbed into the bloodstream.

4
 Advantages tosubouts
altruative

Buca inalso
this
• Avoid hepatic metabolism
• Reduce systemic side eEects
• Rapid drug absorption (plasma proFle similar to IV
bolus)
• Quick onset of action.
• Non invasive
• Lower Dose & hence lower side eEects
• Useful for both systemic and local eEect
• Easy administration for unconscious patients.
• Preferred for systemic delivery of organic and peptide
based drugs.
• Convenient for long term therapy, compared to
parenteral medication.
5
 Limitations
• Loss of eOciency
• Requires narrow range of particle size
• May not be suitable for long term use
• Absorption compatibility
• Dose inaccuracy
• Large wastage
• DiOculty in using the delivery devices correctly.
• Pathologic conditions (cold or allergies) may alter the
nasal bioavailability.
• Inconvenient to patients when compared to oral
delivery systems.
• Nasal cavity provides smaller absorption surface area
when compared to GIT.
6
Anatomy of the lungs
The respiratory tract is divided into 2 main parts, namely;
 Upper tract
 nose
 nasal cavity
 and pharynx. morethanto
 Lower tract
 Larynx QA
 Trachea local
 Bronchi 35
 and lungs. Coral
WIFE

0.5 37
systemic
 most rage
Important

Structure of lungs
ion
naransairesionematose
man
ronchiarregion
ss coca eat
Particles deposited in
easyon
circulation
the alveolar region
ParIcle size greater than 10 um may be taken up by
methane
But o
morethanouindepositinan
pan macrophages and
eliminated via the
lymphatic system or
µ absorbed into the
in
Biggersize tuatara pulmonary circulation
ParIcle size 3-5 um

deposithere
therapy
thisconforsystemic

ParIcle size 0.5-3 um ParIcle size less than 0.5 um

8
are removed in expired air
Disorders and Diseases in the
• Asthma
Respiratory systems
• CysIc Ubrosis
• Pneumonia
• Pulmonary hypertension
• Common cold
• In>uenza

9
 Method of delivery
• Drugs are delivered in the form of aerosol.
• In order to be eOecIve it must:
• Deposit in the appropriate lung region
• Right quanIty
• Overcome the physiological barriers and respiratory defence mechanisms

10
 Factors aOecIng
drug delivery:

oneposit
assure
show can
m ama 1) factors 2)factors aOecIng
aOecIng absorpIon and
deposiIon of metabolism of the
drugs drug

a)physiological b)pharmaceuIcal

11
 i

Physiological factors

 Morphology of lungs (size/structure)In systemic delivery

 Oral vs Nasal breathing Area
 Inspiration Zow rate Absorption barrier thickness
itoweastisinnaiea.ie
ientannaieeas iswino.aeerino

axis manner.sn
Blood supply
 Tidal volume assess
soon
deposition

 Breath holdingmoretime Transport route

deposit
more
cess cess
 Disease states
avergairer
arsioavanaming
Enzymatic activity
timeisonang

 Barriers
 Mucus barrier (rate limiting step)
one
onetime

southern a Mucociliary clearance (self cleaning mechanism)

 Alveolar clearance forsystemiccool

basal
 Exercise its neveiso. noted
deposit

ition
causerreatning.mgqreaitgnian
venison
aensitinm.at
sooner

12
 Pharmaceu2cal factors About product
Important during the design of the device and for
the quality control of its performance. canc to
any
These are:
Aerosol velocity Air>ow becomes slower and less turbulent the
Size
more deeply it penetrates the lungs.
I airflow
Shape roundison upperpart
deposition
The dominant deposiIon mechanism for
Density n aerosol parIcles changes with parIcles of
Physical stability smaller aerodynamic size reaching the deepest
regions.
msn.riiania cni.ms

13
 Absorption & metabolism
wantitto
dissolve systemically
so
pure
• In systemically acting drugs these factors act to deliver
drug to site of action
• In locally acIng drugs these factors act to remove drug from its site of
acIon
• DissoluIon and DiOusion of drug through mucous layer
camera.ttIioo.e
otforc.ca
for e a

4
µ • Mucociliary clearance Goodforsystemic
• Alveolar clearance I i n

bragabsorbinthroatwhattheend
• Other factors axisaromat.cat
if deposit in
train as thisplace
and
• Area sea is
• Barrier thickness
• Blood supply Goodincomer
part
lowerpartdeposition entersystemic
• Region in which the drug is deposited
• Membrane permeability
• Transport route Transenaar the or
Bgaieenionis m echanism transport

• Enzymatic activitymanyenzyme metabolism

msn.pnarmaaaicen.at
Blood
ieoriginBraineseceminatemy 14
 a aweon a ic
maneuvers
is
Need for proper inhala2on therapy
a seem
formulation

mini se
in a
in we us as a in sieis a
Development of inhalant therapy that is safe and
eEective depends on:
The pharmaceutically active molecule
Design of the delivery system and formulation.
Potential to aerosolize the drug in appropriate
manmean
systemic
im a
particle size for uniform distribution tw
in
stow
as eie
Maintain concentration in the lungs enough to
ensure optimum delivery as well as conc s wi

pharmacological eEect.

15
 four afromthis
side
son
Aerosolsboas J mania mixture
lose
a nnaissetter
more
mine
Aerosol preparations are stable dispersions or suspensions of
solid material and liquid droplets in a gaseous medium
(mixture of gas and liquid particles) delivered through
mouth.
 The drugs, delivered by aerosols is deposited in the
airways by three principle mechanisms:
gravitational sedimentation, inertial impaction
(collision), and diAusion.
 Density and diameter of particle inCuence the drug
deposition.
and
come h eated
 Sedimentation is the principal mechanism of
deposition of inhaled aerosols moreparticlesizemorecnn.ae deposition

 Sedimentation is ∝ (particle diameter)2 sizerpensityiswmore

innemore
deposition

 Sedimentation mainly occurs in small airways and

alveoli
 Inertial impaction is inCuenced by particle velocity,
diameter of particle and density of aerosol.
i
 DiAusion is proportional to concentration gradient
 Deposition mechanism
a
naive
 Par7cle size 10-30 um (Impac7on) er
16 a
 Par7cle size 3-5 um (Impac7on, and sedimenta7on)
 Current Technologies for
pulmonary drug delivery

Nebulize pMDIs DPIs

r
Air-jet Ultrasonic

Suspension
Aqueous or solution Dry powder
solutions or of drug but inhaled
suspensions in a volatile
aerosolized propellant
17
 Nebulizer
His
• Air-jet: dispersion and aerosilizaIon is brought about by a high
velocity air stream. oxygen ma E
• Jet nebulizers are connected by
tubing to a compressor, that causes
tame a a

2
compressed air or oxygen to >ow is compress

near dime
we wi ie
at high velocity through a liquid
medicine to turn it into an aerosol,
which is then inhaled by the paIent.
Commonly used for paIents in hospitals who have di^culty in
using inhalers, such as in serious cases of respiratory disease, or
severe asthma a#acks.

18
 nie
eventname

Air Jet Nebulizers (atomizers)

• Jet nebulizers are eOecIve in delivering formulaIons that cannot
be delivered with pressurized metered-dose inhalers (pMDIs) and
dry powder inhalers (DPIs). For instance, anIbioIcs, mucolyIcs,
liposomal formulaIons, and recombinant products, such as
Pulmozyme® InhalaIon SoluIon,
are some of the medicaIons that
can be delivered via jet nebulizers.

19
 Atomizers………

Bymouth

• Usually, the aerosolized medicine is inhaled through a tube-like

mouthpiece, similar to that of an inhaler. SomeImes, the mouthpiece
is replaced with a face mask, similar to that used for inhaled
anesthesia, for ease of use with young children or the elderly.
• Advantages: Generates small parIcles with higher delivery capaciIes
than pMDIs and DPIs in is as six ona a
• Issues: Jet nebulizer that generates a lot more noise (oden 60 dB
during use) and is less portable due to a heavier weight.

20
Ultrasonic nebulizers
• Ultrasonic: dispersion and aerosilizaIon is brought about by the high
frequency sound waves produced by a piezo-electric crystal transducer.
six so

t
aearsonation
www.citsnisnereauen
wave
some

21
 pMDIs (pressurized Metered Dose
HInhalers)
Uses a propellant
(e.g. Hydro>uoroalkanes- HFAs)
similarin a
nationreegrater

Device is composed of:

1) Container a a a
n a
2) Metering Valve: releases a Uxed volume of Deviceuse to increnseating drug
of
aereiners
product during each actuaIon.
3) Elastomer Seal: controls propellant leakage
4) Actuator: permits easy actuaIon of the valve
and provides an oriUce through which the spray is
discharged. 22
Pressurized metered dose W
inhaler e6 t t t if

Can be given in the form of suspension

or solution. Share it
go tomy region
Particle size of less than 5 microns.
It delivers speciFed amount of dose
Small size and convenience.
a
Multi dose capability more than 100
doses available. o
How to use Metered Dose Inhaler (MDI)
h#ps://www.youtube.com/watch?v=fHYTz-ZoRLw

23
 DPIs (Dry Powder Inhalers)

• These devices permit the drug to be delivered to the airways as a dry

powder aerosol.
• They do not require a propellant
• They eliminate the need for paIent coordinaIon of actuaIon and inhalaIon
she
e associated with pMDIs
wi
• The parIcles are travelling at a slower rate, thus excessive drug loss due to
impacIon in the throat is avoided.
a is a.ws onin is mi se estas

24
 case in or u
checkthe
dose
holdingtime

How to use Diskus Inhaler

h#ps://www.youtube.com/watch?v=Kr02is6jVUk

25
Comparison
Inhala2on device
Nebulizers (Jet/Ultrasonic)
Pressurized metered dose
inhalers
Dry powder inhalers
Advantages Disadvantages
No speciUc inhalaIon technique required Time consuming
Aerosolizes most drug soluIons Bulky
Deliver large doses Contents easily contaminated
Suitable for infants Poor delivery e^ciency
Non uniformity in drug delivery
Compact PaIent cooperaIon required
Portable
MulI dose E
Reproducible dosing
High oral deposiIon
Maximum dose 5 mg
No degradaIon of drug
Compact Respirable dose dependent on
Portable inspiratory >ow rate
Easy to use Contains lactose
26
 Applications
 Currently, over 25 drug substances are marketed as
inhalation aerosol products for local pulmonary eEects.

 DiEerent categories include;

 Anti asthamatic drugs: Salbutamol, terbutaline,
 Anti neoplastic drugs: Cyclophosphamide,
Thiophosphamide
 Anti viral drugs: Ribavirin, Acyclovir, Gancyclovir
 AnIbioIcs: Beta lactams, Fluoroquinolones
 AnI-in>ammatory: Nedocromil, crymoglycate
 MucolyIcs: N-acetyl cysteine

27
 References
 Chien Y.W., Su K.S.E., Chang S.F., Nasal Systemic Drug
Delivery, Ch. 1, Marcel-Dekker, New York 1-77.
 Anthony J. Hickey, Physiology of airway. In: Anthony J.
Hickey, editor. Pharmaceutical inhalation aerosols
technology, second edition.vol-54.New York: Marcel
Dekker;1992.p.1-24.
 Paul J. Atkins, Nicholas P. Barker, Donald P. Mathisen, The
design and development of inhalation drug delivery
system. In : Anthony J. Hickey, editor. Pharmaceutical
inhalation aerosols technology, second edition.vol-
54.New York: Marcel Dekker;1992.p.155-181.

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