PULMONARY DRUG DELIVERY
SYSTEMS
AEROSOLS, PROPELLENTS, CONTAINERS
TYPES
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INTRODUCTION
Pulmonary drug delivery is primarily used to treat
conditions of the airways, delivering locally acting drugs
directly to their site of action.
Delivery of anti-asthmatic and other locally acting drugs
directly to their site of action reduces the dose needed to
produce a pharmacological effect, while the low
concentrations in the systemic circulation may also
reduce side-effects.
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The drugs which are administered by pulmonary route
are not only for lungs delivery but it goes to systemic
circulation and produce the effect where it is desired
through out the body.
For Eg. A product containing ergotamine tartrate is
available as an aerosolized dosage inhaler for the
treatment of migraine & Volatile anesthetics, including,
halothane, are also given via the pulmonary route.
In recent years, the possibility of utilizing the
pulmonary route for the systemic delivery of peptides
and other molecules which are not absorbed through the
gastrointestinal tract has also been explored.
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ANATOMY & PHYSIOLOGY OF LUNGS
1. Lungs region
2. Nasopharyngeal region
3. Tracheo-bronchial region
4. Alveolar region
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1) Lung regions: The respiratory tract starts at the nose and
terminates deep in the lung at an alveolar sac. There are a
number of schemes for categorizing the various regions of the
respiratory tract.
2) Nasopharyngeal region (NP region) :This is also referred to
as the “upper airways”, which involves the respiratory airways
from the nose down to the larynx.
3) Tracheo-bronchial region (TB region): This is also referred
to as the “central” or “conducting airways”, which starts at the
larynx and extends via the trachea, bronchi, and bronchioles
and ends at the terminal bronchioli.
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4) Alveolar region: This is also referred to as the
“respiratory airways”, “peripheral airways” or
“pulmonary region”, Comprising the respiratory
bronchioles, alveolar ducts and alveoli .
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ADVANTAGE OF PDDS
Inhaled drug delivery puts drug where it is needed.
It requires low and fraction of oral dose i.e. drug
content of one 4 mg tablet of salbutamol equals to 40
doses of meter doses.
Pulmonary drug delivery having very negligible side
effects since rest of body is not exposed to drug.
Onset of action is very quick with pulmonary drug
delivery.
Degradation of drug by liver is avoided in pulmonary
drug delivery.
In asthma and diabetes requires long term treatment
if it is given by pulmonary drug delivery safety is
maximum because rest of body is not exposed to drug.
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DISADVANTAGE OF PDDS
Low Efficiency of inhalation system
Poor formulation stability for drug
Improper dosing reproducibility
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AEROSOLS
Aerosol is a pressurized dosage forms containing
one or more therapeutic active ingredients which
upon actuation emit a fine dispersion of liquid
and/or solid materials in a gaseous medium.
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COMPONENTS OF AEROSOLS
1. Propellant
2. Container
3. Valve and actuator
4. Product concentrate
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PROPELLANTS
Responsible for developing proper pressure
within the container.
Provide driving force to expel the product from
the container.
TYPES OF PROPELLANTS
(a) Liquefied gases Propellants
(b) Compressed gases Propellants
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PROPELLANTS TYPES
Depending on the route of administration and use,
I) Type-I Propellant A- Liquefied Gas
1) For oral and inhalation (Fluorinated hydrocarbons)
• Tri-chloro-mono-flouro methane (propellant 11)
• Di-chloro di-fluro methane (propellant 12)
2) Topical Pharmaceutical aerosols (Hydrocarbons)
• Propane
• Butane
II) Type-II Propellant B – Compressed Gas Propellants
Compound gases
• Nitrogen
• Carbon di-oxide
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LIQUEFIED GAS PROPELLANTS
Exist as liquids under pressure.
Because the aerosol is under pressure propellant
exists mainly as a liquid, but it will also be in the head
space as a gas.
The product is used up as the valve is opened, some of
the liquid propellant turns to gas and keeps the head
space full of gas.
In this way the pressure in the can remains
essentially constant and the spray performance is
maintained.
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CHLORO FLUORO CARBONS
Advantages
• Chemical inertness
• Lack of toxicity
• Non flammability.
• Lack of explosiveness.
Disadvantages
• High cost
• It depletes the ozone layer
Examples:
Trichloromonofluoromethane – Propellant 11
Dichlorodifluoromethane – Propellant 12
Dichlorotetrafluoroethane – Propellant 114
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HYDROCARBONS
Can be used for water based aerosols and topical use.
Advantages
• Inexpensive
• Excellent solvents
• It does not cause ozone
Disadvantages
• Inflammable
• Unknown toxicity produced
Example
Propane – Propellant A-108
Isobutane – Propellant A-31
Butane – Propellant A-17
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HYDROFLUORO CARBONS AND
HYDRO CHLORO FLUORO CARBONS
These compounds break down in the atmosphere at faster rate
than cfcs.
Lower ozone destroying effect
Advantages:
Low inhalation toxicity
High chemical stability
High purity
Not ozone depleting
EXAMPLES:
heptafluoro propane (hfa-227)
tetrafluoroethane (hfa-134a)
difluoroethane – propellant 152a
Disadvantages
Poor solvent and High cost
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COMPRESSED GAS PROPELLANTS
Compressed gas propellants occupy the head space above
the liquid in the can.
When the aerosol valve is opened the gas ‘pushes’ the
liquid out of the can.
The amount of gas in the headspace remains the same
but it has more space, and as a result the pressure will
drop during the life of the can.
Spray performance is maintained however by careful
choice of the aerosol valve and actuator.
Examples: Carbon dioxide, Nitrous oxide and Nitrogen
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CONTAINERS
They must be able to withstand pressures as high as
140 to 180 psig (pounds per sq. inch gauge) at 130 ° F.
AEROSOL CONTAINERS
A. Metals
i. Tinplated steel
ii. Aluminum
iii. Stainless steel
B. Glass
I. Uncoated glass
II. Plastic coated glass
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TIN PLATED STEEL CONTAINERS
It consist of a sheet of steel plate, this sheet is coated
with tin by electrolytic process.
The coated sheet is cut into three pieces ( top , bottom
and body) .
The top, bottom are attached to body by soldering.
When required it is coated with organic material
usually oleoresin, phenolic ,vinyl or epoxy coating.
Welding eliminates soldering process, Saves
considerable manufacturing time and decreases the
product/container interaction.
Recent developments in welding include Soudronic
system and Conoweld system.
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ALUMINIUM CONTAINERS
Used for inhalation and topical aerosols.
Manufactured by impact extrusion process.
Light in weight, less fragile, Less incompatibility due
to its seamless nature.
Greater resistance to corrosion .
Pure water and pure ethanol cause corrosion to Al
containers.
Added resistance can be obtained by coating inside of
the container with organic coating like phenolic ,
vinyl or epoxy and polyamide resins.
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STAINLESS STEEL CONTAINERS
Used for inhalation aerosols
Advantage :
Extremely Strong.
Resistant to many materials.
No need for internal coating.
Disadvantage :
o Costly
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GLASS CONTAINERS
These containers are preferred because of its Aesthetic
value and absence of incompatibilities.
These containers are limited to the products having a
lower pressure (33 psig) and lower percentage of the
propellant.
Used for topical and MDI aerosols.
Two types of glass aerosol containers
Uncoated glass container:
➢ Less cost and high clarity and contents can be viewed at all
times.
Plastic coated glass containers:
➢ These are protected by plastic coating that prevents the
glass from shattering in the event of breakage.
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VALVES
To delivered the drug in desired form.
To give proper amount of medication.
Not differ from valve to valve of medication in
pharmaceutical preparation.
Types
– Continuous spray valve
– High speed production technique.
– Metering valves
Dispersing of potent medication at proper dispersion/
spray approximately 50 to 150 mg ±10 % of liquid
materials at one time use of same valve.
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VALVE COMPONENTS
Ferrule or mount cap
Valve body or housing
Stem
Gasket
Spring
Dip tube
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ACTUATORS
These are specially designed buttons which helps
in delivering the drug in desired form i.e., spray,
wet stream, foam or solid stream.
TYPES OF ACTUATORS:
• Spray actuators
• Foam actuators
• Solid steam actuators
• Special actuators
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SPRAY ACTUATORS:
▪ It can be used for topical preparation, such as antiseptics, local
anesthetics and spray on bandages etc.
▪ It allows the stream of product concentrate and propellant to pass
through various openings and dispense as spray.
FOAM ACTUATORS:
▪ It consist of large orifice which ranges from 0.070—0.125 inch.
SOLID STREAM ACTUATORS:
▪ These actuators are required for dispensing semi solid products such
as ointments .
SPECIAL ACTUATORS:
▪ These are used for a specific purpose.
▪ It delivers the medicament to the appropriate site of action such as
throat, nose, dental and eyes etc.
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RECENT ADVANCES IN PULMONARY
DRUG DELIVERY DEVICES
Following types of inhalation devices are present
1. Inhalation drug delivery system by ‐ nebulizer
2. Inhalation drug delivery system by – metered
dose inhalers
3. Inhalation drug delivery system by ‐ dry
powder inhalers
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1. NEBULIZER
Nebulizers used today for drug delivery to the respiratory tract and are
particularly useful for the treatment of hospitalized and
nonambulatory patients.
Mainly there are two general types of nebulizer systems,
The ultrasonic and
The air jet
The ultrasonic nebulizer uses a piezoelectric crystal, vibrating at a high
frequency (usually 1–3 MHz), to generate a fountain of liquid in the
nebulizer chamber; the higher the frequency, the smaller the
droplets produced
The jet nebulizer functions by the Bernoulli principle by which
compressed gas (air or oxygen) passes through a narrow orifice,
creating an area of low pressure at the outlet of the adjacent liquid
feed tube. This results in the drug solution being drawn up from the
fluid reservoir and shattering into droplets in the gas stream.
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Advantage:
The nebulizer can transport more drugs to the lungs than
MDI or DPI.
The treatment of acute asthma in an emergency care unit.
Rapid absorption, higher bioavailability, therefore, lower
doses .
Avoidance of liver first pass metabolism.
Avoidance of metabolism by the gastrointestinal tract.
Disadvantage:
Lack of possibility
Higher costs
The need for higher drug doses to achieve a therapeutic
result
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METERED DOSE INHALER (MDI)
Used for the treatment of respiratory diseases such as
asthma and COPD.
They can be given in the form of suspension or
solution.
Particle size of less than 5 micros.
Used to minimize the number of administrations
errors.
It can be delivery measure amount of medicament
accurately.
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Advantage of MDI Disadvantage of MDI
▪ It delivers specified ▪ Difficult to delivery
amount of dose. high doses.
▪ Small size and ▪ There is no
convenience. information about the
number of dose left in
▪ Usually inexpensive
as compare to dry the MDI
powder inhalers and ▪ Accurate co-ordination
nebulizers. between actuation of a
▪ Quick to use. dose and inhalation is
essential
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DRY POWDER INHALER (DPI)
DPIs are bolus drug delivery devices that contain solid drug
in a dry powder mix (DPI) that is fluidized when the patient
inhales.
DPIs are typically formulated as one-phase, solid particle
blends. The drug with particle size of less than 5µm is used.
Dry powder formulations either contain the active drug
alone or have a carrier powder (e.g. lactose) mixed with
drug to increase flow properties of drug.
DPIs are a widely accepted inhaled delivery dosage form,
particularly in Europe., where they are currently used by
approximately 40% of asthma patient
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Advantage
Propellant-free.
Less need for patient co-ordination.
Less formulation problem
Dry powders are at a lower energy state, which
reduces the rate of chemical degradation
Disadvantage
Delivery on patient’s inspiratory flow rate and profile.
Device resistance and other design issues.
Greater potential problems in dose uniformity.
More expensive than pressurized metered dose
inhalers.
Not available worldwide
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TODAY THERE ARE ESSENTIALLY TWO TYPES OF
DPIS
Unit-Dose Devices
Single dose powder
inhalers are device in
which a powder
containing capsule is
placed in a holder.
The capsule is opened
with in the device and
the powder is inhaled.
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Multi dose Device
This device is truly a
metered-dose powder
delivery system. The
drug is contained with
in a storage reservoir
and can be dispensed
into the dosing
chamber by a simple
back and forth
twisting action on the
base of the unit
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QUESTIONS
Write about pulmonary drug delivery system
(5M) 2times
Explain formulation and evaluation pulmonary
drug delivery system (20M)