2. 1. Introduction
2. Anatomy of respiratory tract
3. Evaluation of pulmonary functions
4. Mechanisms of drug absorption
5. Particle disposition
6. Factors affecting particle disposition
7. Devices used for delivery of drug
8. Routes of adminstration
9. Advantages of pulmonary drug delivery system
10. Disadvantages of pulmonary drug delivery system
3. •Pulmonary drug delivery system deals with the
administration of therapeutic agent directly to the
lungs via the nasal or oral route.
•This system is more preffered route for many
systemically active agents, especially in case of
drugs are subjected to gastrointestinal degradation.
Eg: insulin degradation by proteases, if orally
administered.
4. •In olden days generally it is only used for local
action and immediate action in treatment of
asthma, chronic obstructive lung disorder.
•The use have increased drastically because of its
painless delivery and non invasive method for
delivery into systemic circulation.
•It also prevents first pass liver degradation of the
drug.
•Ephedrine was the first drug to be used as local
action aerosol for use in respiratory tract.
5. •Respiratory tract mainly includes nose, pharynx,
larynx, trachea, bronchi and lungs.
•Each lung is enclosed by two layers of pleura. Two
layers of pleura are viseral and parietal layers.
•Pleural cavity is present between two layers of pleura.
This space is filled with pleural fluid which act as a
lubricant.
•Trachea bifurcates into main primary bronchus which
enters the lungs and divides in turn to secondary
bronchi and finally tertiary bronchi which divides and
terminates in alveoli.
6. •Alveoli is termed as respiratory unit as it is the site
where the exchange of gases occurs.
•This respiratory unit includes respiratory
bronchioles, alveolar ducts, alveolar sacs and
alveoli.
7.
8. They are used to evaluate diseases that affect heart and lung function to screen
persons at risk for pulmonary disease, also used to monitor the effectiveness of
drug with known pulmonary toxicity
•Peak flow measurements:- in this test subject inhale completely then expire
forcefully into a peak flow meter which records the maximal flow of expiration.
•Flow expiratory flow measurements:- in this subject starts of TLC(total lung
capacity) and exhales as rapidly and as completely as possible into mouthpiece of a
spirometer which records the volume of air expired overtime.
It is calculated by taking the ratio of
FEV1.0/FVC
Where FEV1.0= volume of air exhaled in first second
FVC = total volume exhaled (force vital capacity)
•Forced expiratory flow rate:- measurements of force expiratory flow rate(FEV
25-75%) which represent the average flow rate determined over the mid portion of
the expiration.
•Lung volumes:- measurements of lung volumes by spirometer, gas dilution can
yield valuable information about lung function.
11. Mechanism of drug particle depends on nature of drug
particles. Mainly there are three mechanisms through which the
drug absorbs.
• Drug diffusion through alveoli.
• Paracellular absorption with help of carriers.
• Phagocytosis of drug particles.
12. For the drug to show required action it has to get deposited in
site of action. This depends on ability of drug to penetrate the
respiratory tract. Particle size plays a key role in deposition.
Particle deposition in lungs is by three main mechanisms.
•Gravitational sedimentation: depends mainly on particle
size, density and resident time in airways. Observed mainly in
particles of size 0.5-3µm.
•Inertial impaction: seen mainly in particles of size greater
than 10µm and is common in upper airways.
•Brownian diffusion: this is seen mainly due to collisions and
bombardment of small particles by molecules in respiratory
tract. Very frequent in particles smaller than 0.5µm
13. Type of
mechanism
Particle size
Particle
density
Breathing
cycle period
Flow rate of air
Brownian
diffusion
Decreases with
size
Independent of
density
Increases with
time
Independent of
flow rate
Gravitational
sedimentation
Increases with
size
Independent of
density
Increases with
time
Independent of
flow rate
Inertial
impaction
Increases with
size
Increases with
density
Increases with
time
Independent of
flow rate
14. 1. Particle size
2. Particle velocity
3. Particle density
4. Flow rate of air
5. Breathing cycle period
15.
16. Devices used to deliver the drugs are commonly termed as
aerosols. These are 2 phase systems containing solids or liquids
suspended in gaseous system. These are prepared by
atomization.
Various devices for drug delivery are:-
1. Pressurised meter dose inhalers(MDI)
2. Dry powder inhalers (DPI)
3. Nebulizers
17. •Most of the commonly used device by out patients.
•Delivery of the drug is by propellants which deliver with high
velocity.
•Mainly used propellants are chlorofluorocarbons and hydrofluoro
alkanes.
•It emits an aerosol driven by propellants like CFCs though nozzle at
the velocity greater than 30m/s
•10-20% of drug reaches lungs by this method while 50-80% remain
in oropharynx itself and depends on the patient’s itself, his breathing
pattern and inspirational flow rate.
•Drugs administered using this technique are
beclomethasone, fluticasone.
Mechanism of drug delivery is by sedimentation or diffusion.
18.
19. • In this only dry powders are delivered and propellants are not
used.
•These contain micronised drug substance with or without
carrier.
•Using this device, 12-40% of drug reaches the lungs and 20-25%
remains in this device.
•The drug disintegration rate and effectiveness of the DPIs are
controlled by humidity, changes in temp. and inspiratory rate.
•Mechanism of drug deposition is by impactation.
•Drugs delivered by this device are
salmeterol(brand name: Serevent)
formoterol(brand name: foradil)
22. •These are the oldest techniques in pulmonary drug delivery.
•Nebulizers are effective, easy to use and inexpensive.
Two type of nebulizers are:-
1. Jet nebulizers
2. Ultrasonic nebulizers
Jet nebulizers
• Works on bernoulli’s principle.
• In this, low pressure is created by compressed gas through which
solution rushes out and is atomized to give fine droplets.
eg:- acron 1 and acron 2
24. In tracheal route :-
•majorly used for asthma drugs.
•Effective concentrations are not reached
Intravenous route :-
•Used only in urgency cases as rapid onset of action
is seen.
•Delivery to lungs is accurate because of high
pulmonary vasculature.
25. 1. Avoids first pass metabolism which is seen extensively in oral
route.
2. Large surface area of lungs favours the high absorption of drug or
medicament without loss of drug.
3. High blood supply favors complete and rapid absorption.
4. Accurate dose of drug is sufficient for required action.
5. It delivers drug without pain
6. It is non-invasive method for delivery of drugs into blood stream
which can be administered only by injections like
proteins(insulin) and peptides.
7. Effective drug targeting can be achieved.
8. Avoids GI difficulties like poor solubilities, degradation, GI
irritation.
9. Rapid onset of action.
26. 1. Effective only for local treatment.
2. Devices used to delivery the delivers only
upto 20% of emitted dose into lungs.
3. Presence of aerodynamic filters in lungs
obstructs the complete passage of drugs
into alveoli.
4. Presence of mucous may divert the delivery
route of drug particles.
5. Large amounts of wastage are caused.
