Aerosol science and technology

Reference: Aulton’s Pharmaceutics: The Design and Manufacture of Medicine

Mohammad Ashraful Islam

Lecturer
Department of Pharmacy
University of Asia Pacific
 Pulmonary route of drug delivery

The delivery of the drug through the respiratory tract is called pulmonary drug delivery. The main
purpose of this drug delivery route is the inhalation of drug formulation through mouth and the further
deposition of inhaled pharmacological agent in lower airways.

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.

2
 Anatomy of respiratory system

The human respiratory system is divided into upper and lower

respiratory tracts
• The upper respiratory system consists of the nose, nasal
cavities, nasopharynx, oropharynx and larynx.
• The lower respiratory tract consists of the trachea, bronchi,
and alveoli, which are composed of respiratory tissues.
• The left and right lungs are unequal in size. The right lung is
composed of three lobes, while the smaller left lung has two
lobes

3
Particle deposition in respiratory system

• Larger particles deposit in the upper airways or

mouth and throat, whereas smaller particles deposit
in the alveolar region.
• Particles <1 μm can be exhaled, thereby reducing
deep-lung deposition.
• Since particle size affects the lung deposition of an
aerosol, it also can influence the clinical
effectiveness of a drug.

4
Mechanism of particle deposition in respiratory system

Three different mechanisms:

1. Inertial impaction (particle size > 5 μm)
2. Gravitational Sedimentation (particle size 1–8 μm)
3. Brownian Diffusion (particle size <1 μm in diameter)

5
 1. Inertial impaction

This is the dominant deposition mechanism for particles >1 µm in the upper tracheobronchial
regions. A particle with a large momentum (the product of mass and velocity) may be unable to
follow the changing direction of the inspired air as it passes the bifurcations and as a result will
collide with the airway walls. Impaction therefore usually occurs near the bifurcations.

The probability of inertial impaction will be dependent upon particle momentum, thus particles with
larger diameters or higher densities and those traveling in airstreams of higher velocity will show
greater impaction.

6
 2. Gravitational sedimentation

This is particle deposition resulting from settling under

gravity. It becomes increasingly important for particles
that reach airways where the airstream velocity is
relatively low, e.g. the bronchioles and alveo­lar region.
The fraction of particles depositing by this mechanism
will be dependent upon the time the particles spend in
these regions.

7
 3. Brownian diffusion

This is of little significance for particles >1 µm. Particles below this size are displaced by a random
bombardment of gas molecules, which results in particle collision with the airway walls. The
probability of particle deposition by diffusion increases as the particle size decreases. Brownian
diffusion is also more prevalent in regions where airflow is very low or absent, e.g. in the alveoli.

8
 Parameters affecting particle deposition

• Aerodynamic particle behavior: Size, density, hygroscopicity, shape, charge.

• Breathing pattern: For any given particle size, increasing depth of inhalation produces
increase in deposition
• Airway anatomy and morphology of patient
• Disease: Lung diseases are often accompanied by airway narrowing (e.g. asthma), change in
lung compliance, and/or mucus overproduction

9
 Advantages & disadvantages of pulmonary drug delivery
Locally acting drugs
Advantages
 The dose needed to produce a pharmacological effect can be reduced.
 Low concentrations in the systemic circulation are associated with reduced systemic side effects.
 Rapid onset of action.
 Avoidance of gastrointestinal upset.
 Avoidance of intestinal and hepatic first-pass metabolism.

Disadvantages
 Oropharyngeal deposition may give local side-effects.
 Patients may have difficulty using the delivery devices correctly.
 Drug absorption may be limited by the physical barriers, e.g. mucus layer.
 Mucociliary clearance reduces the retention time of drugs within the lungs. 10
 Advantages & disadvantages of pulmonary drug delivery
Systemic drugs
Advantages:
 The lungs offer a very large surface area for drug absorption.
 The permeability of the lung membranes towards many compounds is higher than that of the small
intestine and other mucosal routes.
 The highly vascular surface of the AV region promotes rapid absorption and onset of action.

Disadvantages:
 Various factors affect the reproducibility of drug delivery (lack of drug uniformity)
 Complex delivery devices are required which may be inefficient and difficult to use
 Drug absorption may be limited by the physical barriers, e.g. mucus layer.
 Mucociliary clearance reduces the retention time of drugs within the lungs.
11
 Aerosol dosage form

Definition
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.

12
 Types of Aerosol dosage form

1. Space spray: These are finely divided sprays having particle size upto 50 µ. e.g. insecticides,
disinfectants and room deodorizers.

2. Surface coating spray: These are also sprays but disperse particles are coarse with size upto
200 µ. They produce a wet coat when sprayed on a surface. e.g. hair sprays, personal
deodorant, powder sprays and topical medicament sprays.

3. Foam: These are produced by rapid expansion of propellants through an emulsion. Hence, the
product comes out in the form of a foam or froth. e.g. shaving cream and vaginal product

13
 Advantages of aerosol delivery system

 Convenient and ready-to-use.

 Can dispense product in small or large doses and can jet the product over long distances.
 Aerosols have a long shelf life.
 They are hermetically sealed and cannot be contaminated by bacteria or dust.
 It is leak proof and contents do not evaporate and the product's characteristics will not
change over the lifetime of the product.
 Faster Onset of action.
 No manual/ direct contact with the medicament.
 Avoid the first pass metabolism.
 Protect the photosensitive medicaments and oxygen sensitive material.

14
 Disadvantages of aerosol delivery system

 Costly.
 Allergic in some cases.
 Explosive.
 Some formulation is difficult.
 Difficult disposal of empty aerosol containers.
 It is difficult to prepare aerosols dosage form of insoluble drug.
 If long term used of propellant it is produced toxic effect.
 Some time its contaminate drugs by its trace metal that presence in container

15
 Types of inhaler devices

There are different kinds of inhaler devices for drug administration

1. Metered dose inhalers (MDI)

2. Dry powder inhalers (DPI)
3. Nebulizers

16
 Pressurized metered-dose inhaler (pMDI)

In pMDIs, drug is either dissolved or suspended in

liquid propellant(s) together with other excipients,
including surfactants, and presented in a pressurized
canister fitted with a metering valve.

A predetermined dose is released as a spray on

actuation of the metering valve.

Pressurized metered-dose inhaler

17
 Pressurized metered-dose inhaler (pMDI) Cont….

Advantages of MDI:
a) It delivers specified amount of dose.
b) Portable and compact.
c) Quick to use, no contamination of product.
d) Dose reproducibility is high.

Disadvantages of MDI:
e) Low lung deposition; high pharyngeal deposition
Pressurized metered-dose inhaler f) Coordination of MDI actuation and patient inhalation is
needed.
18
 How does an pMDI work?
The product is dissolved or suspended in a liquid solvent. A liquid gas is
usually used as a propellant.

In a typical aerosol, some of the propellant exists as a gas under pressure above
the product. This gas pushes down on the liquid, forcing it up through the dip
tube and out the valve when it is opened. The liquid is a mixture of product and
liquefied propellant. As it is released, the gas evaporates from the liquid in the
container gas.

When the liquid mixture is released from the aerosol, the liquid propellant
becomes a gas and helps break up the product into a fine mist. In foams like
shaving cream, the liquid gas forms bubbles, making the product expand as it
is released from the aerosol.
19
Components of an Aerosol

An aerosol product consists of the following component parts:

1. Propellant
2. Container
3. Valve and actuator
4. Product concentrate

20
 1. Propellant

Propellants are responsible for developing proper pressure within the container and providing the driving
force to expel the product from the container.

There are mainly two types of propellants -

A. Liquefied gas propellants
1. Chlorofluorohydrocarbon
2. Hydrocarbons
B. Compressed gas propellants

21
 1. Propellant Cont…
A. Liquefied gas propellants: Liquefied gas propellants are exits as liquids under pressure but when valve is opened
they convert into gas. It is divided into two sub types –

1. Chlorofluorohydrocarbon: It is mainly used for oral and inhalation 2. Hydrocarbons: It can be used for water
preparation. Examples are trichloromonofluoromethan (Propellant aerosols and topical use. Example propane
11), dichlorodifluoromethane (propellant 12), (propellant A-108), Butane (propellant A-
dichlorotetrafluoromethane (propellant 114). 17).
Advantages: Advantages:
• Chemical inertness • Inexpensive

• Lack of toxicity • Excellent solvent

• Non flammability • It does not cause ozone layer

• Lack of explosiveness depletion

Disadvantages Disadvantages:

• High cost • Inflammable

• • Unknown toxicity may be produced22

It depletes the ozone layer.
 1. Propellant Cont…

B. 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 by careful choice of the aerosol
valve and actuator.
• Examples: Carbon dioxide, Nitrous oxide and Nitrogen.

23
 2. Container

Container provides optimal conditions to store the product to be sprayed. Containers must be able to
withstand pressures as high as 140 to 180 psig (pounds per sq. inch gauge) at 130°F.
Containers may be made of –
A. Glass container
1. Uncoated glass
2. Plastic coated glass
B. Plastic container
C. Metals container
1. Tinplated steel
2. Aluminum
3. Stainless steel

24
 2. Container Cont…
A. Glass container: These types of container are used when low pressure and low amount of propellant are
used. In this type of container no corrosion problem are seen. This type of container is used in topical &
MDIs aerosols. It is also sub divided into Coated & Uncoated.
B. Plastic container: It is highly permeable to vapor so may be chance of oxidative degradation in
formulation.
C. Metal container: This types of container are subdivided into three types
1. Tin plated steel: It consist of a sheet of steel plate, this sheet is coated with tin by electrolytic
process.
 Tin are coated by electrolytic process.
 Three pieces of sheet
 Joined by soldering.
 Use of vinyl or epoxy coating to prevent of reaction due to soldering.
25
 Use for topical aerosols
 2. Container Cont…
C. Metal container: Continued…
2. Stainless steel
 No coating required
 Highly inactive
 Vinyl resins are not used in inside coating because of heat sterilized so epoxy is widely used.
 It is very costly it is only its disadvantage.
 It is used for mainly inhalation aerosols.
3. Aluminium
 It is very light weight.
 The combination of ethanol and propellant 11 in an aluminium container produces hydrogen,
acetyl chloride, aluminium chloride, propellant 21 and other corrosive products.
 It is used both types of aerosols MDIs & topical aerosols.
26
 3. Valve and Actuator Cont…

Valve: Valve assists to release the product from the container in the
desired form when it is opened. There are two forms of valves
1. Conventional or continuous spray valve: Continuously expels the
product as long as the valve is opened. It is used mainly tropical
aerosols.
2. Metered-dose valve: Delivers a predetermined quantity of the
product when the valve is opened. Metered-dose valve has a
specially designed chamber in the valve housing which holds a
certain volume of the product concentrate for releasing outside
ensuring delivery of a definite dose. These are used in metered dose
inhalers.
27
 3. Valve and Actuator Cont…

Basic parts of a valve assembly: It is consists of different parts as shown below –

28
 3. Valve and Actuator Cont…
Functions of the parts of a valve assembly

29
3. Valve and Actuator Cont…
Mechanism of aerosol valve action

30
 3. Valve and Actuator Cont…

Actuator
An actuator is a device attached to an aerosol valve stem,
which when depressed or moved, opens the valve and
directs the spray containing the drug preparation to the
desired area.

Actuator ensures that –

 the stem can be pressed down conveniently and the
valve opened easily
 the product is delivered in the proper and desired
form. 31
 3. Valve and Actuator Cont…
Types of actuators:
1. Spray actuators: It is used for topical preparation
2. Foam actuators: It consists of large orifice 0.070-
0.125 inch
3. Solid stream actuator: It is used for semi solid
preparation.
4. Special actuator: It delivers the medicaments to
appropriate site of action such as throat, nose, eye etc.
5. Mechanical breakup actuators (MBU): A special
classes of actuators are called mechanical breakup
(MBU) actuators. They have a swirl chamber and can
reduce the droplet size of the product.
32
 4. Product Concentrate

Formulations of product concentrate of pMDI

Aerosol products consist of two components –
1. Volatile: The volatile portion includes single propellant or a mixture of propellant and volatile
solvents.
2. Non-volatile: The non-volatile portion includes active ingredients, non-volatile solvents and
dispersing agents.

33
 4. Product Concentrate Cont….
Types of aerosol product concentrate systems

34
 4. Product Concentrate Cont….

A. Homogenous Aerosol Systems (Solution aerosol system): In this system API is dissolved in pure
propellant or mixture of propellant and solvents. These are relatively easy to formulate provided the
ingredients are soluble. The commonly used solvents are ethyl alcohol, polyethylene glycol, di-propyl
glycol, ethyl acetate, hexylene glycol, acetone, glycol ether, etc. The particle of spray can be 5 to 10
μm for inhalation aerosol, whereas 50 to 100 μm for topical aerosol.

35
 4. Product Concentrate Cont….

B. Heterogeneous Aerosol System

1. Suspension system: The drug substances that are insoluble in the propellant or mixture of propellant
and solvent can be suspended in the propellant vehicle. When the valve is dispersed, the suspension is
emitted followed by rapid vaporization of propellant leaving behind the finely dispersed active
ingredients. This suspension system has been formulated for drugs, such as anti-asthmatic, steroid,
antibiotic etc. The major problems associated with these systems include caking agglomeration,
particle size growth and clogging of the valve.
Important features
Moisture content of ingredients should be kept below 200 to 300 ppm.
Particle size should be 1 to 5 μm and for topical aerosol 40 to 50 μm.
API must have sufficient solubility in body fluids.
The density of the propellant and API should be nearly equal to reduce the rate of sedimentation. 36
 4. Product Concentrate Cont….

B. Heterogeneous Aerosol System

2. Emulsion aerosols: Emulsion aerosols consist of active ingredients, aqueous or a nonaqueous vehicles,
surfactant and propellant. When the propellant is in the internal phase, typical foam is emitted. When the
propellant is in the external phase, the product is dispensed as a spray. The different types of emulsion
aerosols are described below –
• Aqueous stable foams: It contains propellant in the concentration of 3 to 4%. It produces a dry
spray.
• Nonaqueous stable foams: It can be formulated through the use of various glycols, such as
polyethylene glycol.
• Quick breaking foams: In this system, the propellant is in the external phase. When dispensed, the
product is emitted as foam which then collapse into a liquid.
37
• Thermal foams: These are used to produce warm foam for shaving.
 Manufacturing of pMDIs

Manufacturing of pMDIs
Manufacturing of aerosols are intimately connected with filling and packaging. The industrial
manufacturing processes of aerosols involve semiautomatic or automatic machines.
Manufacturing of aerosols can be divided into two stages –
Stage 1: Preparing the product concentrate (solution, suspension, emulsion etc.) which is conducted
following standard procedures for manufacturing of various dosage dorms.
Stage 2: Addition of propellant or propellant blends with the product concentrate with subsequent filling
and sealing of the container. This can be done following two methods:
a. Pressure filling method
b. Cold filling method

38
 Manufacturing of pMDIs Cont…

a. Pressure filling method: The product concentrate

is filled in the container which is then sealed by the
valve. Then the propellant is filled in the container
at high pressure either through the valve (TTV) or
by some other modified ways.

b. Cold filling method: The product concentrate and

the propellant are chilled at very low temperature
below the boiling point of the propellants (–30oF to
–40oF). Then, they are filled in a previously chilled
container which is then sealed by the valve.
39
 Manufacturing of pMDIs Cont…

Pressure filling method

Essentials steps and associated machineries for this procedure are –
1. Concentrate filler: Fills the proper amount of product concentrate into the empty cans.
2. Valve placer: Sets the valves in proper orientation and places them onto the open mouth of the can.
3. Purger and vacuum crimper: Pulls out the air form the can by applying vacuum and crimps the
valves on the cans.
4. Propellant filler: Fills the proper amount of propellant through the valve stem under increased
pressure.
5. Leak tester: The cans are submerged in hot water at 130oF to test for any possible leakage.
6. Actuator and cap placer: Places the actuator and protective cap onto the dried container.

40
 Manufacturing of pMDIs Cont…

Pressure filling method Cont….

Flow charts of pressure filling process of aerosol manufacturing

41
 Manufacturing of pMDIs Cont…

Cold filling method

Essentials steps and associated machineries for this procedure are –
1. Concentrate filler: Fills the proper amount of chilled product concentrate into the chilled empty cans.
2. Propellant filler: Fills the proper amount of chilled propellant into the aerosol cans.
3. Valve placer: Sets the valves in proper orientation and places them onto the open mouth of the cans.
4. Valve crimper: crimps and seals the valves on the cans.
5. Leak tester: The cans are submerged in hot water at 130oF to test for any possible leakage.
6. Actuator and cap placer: Places the actuator and protective cap onto the dried container.

42
 Manufacturing of pMDIs Cont…

Cold filling method Cont…

Flow charts of cold filling process of aerosol manufacturing

43
 Manufacturing of pMDIs Cont…

Comparison between the different steps of pressure filling method and cold filling method of aerosol
manufacturing

44
 Manufacturing of pMDIs Cont…

Pressure filling method is preferred over cold filling method

Pressure filling method is preferred over cold filling method and widely used because Pressure filling
method has some limitations, most of which have been overcome due to technological advancements but
the limitations of cold forming methods haven’t overcome
The limitations of cold filling method of aerosol manufacturing are –
1. Cold filling cannot be applied for aqueous formulations (at the working temperature, water will
become ice).
2. Chance of moisture contamination of the product is more due to low temperature.
3. Loss of propellant due to evaporation is more as the can is sealed after the propellant is added. This
also increases chance of fire hazards and explosion with use of hydrocarbon propellants.
4. Physical stability of suspension and emulsion systems may be lost at low temperature.
45
 Manufacturing of pMDIs Cont…

Pressure filling method is preferred over cold filling method Cont…

The limitations of Pressure filling method, which have been overcome due to technological advancements
–
1. Basically, rate of filling by pressure is slow but now high-speed commercial filling machines are
available. The ‘under the cup / cap’ (UTC) mode of propellant filling has greatly increased the
efficiency of pressure filling method.
2. It was only applicable for normal conventional valves and not for metered valves having greater
complexity in design. Now, specially designed containers and valve systems are available for use with
MDIs which can be handled without problem during the pressure filling process.

46
 Manufacturing of pMDIs Cont…

Under the cup (UTC) pressure filling

This is a technological advancement of TTV mode of filling.
1. Container filled with product concentrate
2. The gassing station seals tightly on the container top.
3. The valve is lifted slightly by vacuum.
4. The propellant delivered inside the container.
5. The valve assembly placed back and crimped onto the container.
6. The container is then ready for use.

47
 Manufacturing of pMDIs Cont…

Bag-on-valve (BOV) aerosol technology

BOV is an innovative technology that offers significant benefits over traditional aerosols. Important
features are:
1. No harmful or flammable propellants. Use only compressed air or nitrogen to propel the product.
2. Product is isolated in an air tight aluminium bag inside the can and remains separated from the gas.

48
Quality control test/Quality Evaluation of MDI (aerosols) Cont…

Test for the quality evaluation of MDI can be divided into –

A. Raw Material quality control
B. In process quality control
C. Quality control of finished product

49
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

A. Raw Material quality control: It includes the tests for following -

1. Propellants: For propellants following parameters should be investigated –

• Identification test by GC or IR spectroscopy
• Vapor pressure
• Density
• Purity
• Non-volatile residue
• Moisture content
• Composition or blend ratio in case of propellants blend

2. Containers, Valves, Actuators and Dip Tubes: Acceptability and performance tested by visual inspection or by adopting suitable

test method. The objective of this test is to determine magnitude of valve delivery & degree of uniformity between individual
50
valves.
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

B. In process quality control:

• Quality specifications of product concentrate: It is very important to rectify any mistake which occurred during
production
• Pressure, temperature and weight of the product concentrate inside the mixing tank should be monitored during
filling the container.
• Leak test: It is done to identify any possible leakage in the container or valve assembly. It is done by immersing
the containers in water bath at high temperature.
• Weight variation: Weight of the filled container checked to meet the fill weight specification.

51
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

C. Quality control of Finished product

1. Flammability and combustibility

• Flash point: The temperature at which the vapor of an aerosol system
ignites is termed as the flash point. This is an important parameter to be
determined for topical aerosols containing hydrocarbon propellants
which are highly inflammable and catches fire easily. It is determined
by using slandered ‘Tag Open Cup’ apparatus. The aerosol product is
first chilled to -25oF and transferred into the apparatus. Then the
temperature is increased slowly to determine the ignition temperature.

52
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

C. Quality control of Finished product Cont….

Flame extension: It is defined as the extent of increase of an open flame upon spraying an aerosol over it for a specified
time. The product is sprayed on a flame for 4 seconds. The length of extension of the flame is measured with a ruler.

2. Physiochemical characteristics:
• Vapor pressure: Pressure within the container should be determined since excessive pressure variation indicates
presence of air in the headspace. It is determined by pressure gauge or can-puncturing device.

• Moisture content: Determined by Karl Fischer method or GC.

• Identification of propellants: It can be done by GC or IR spectroscopy.

• Concentrate-propellant ratio: Determined by adopting appropriate analytical procedure.

53
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

C. Quality control of Finished product Cont….

3. Performance
• Aerosol valve discharge rate: Product discharged from the container per unit time.
• Spray pattern: The spray pattern should meet the specific requirements of the product. The product
is sprayed on a paper coated with dye and talc. The dye may be water soluble or insoluble depending
on the nature of the aerosol product.
• Dosage with metered valves: Dose delivered per actuation (puff) which should be exact and
reproducible.
• Net content: Weight of the contents should be uniform from container to container.
• Foam stability: Visual inspection, investigated by instruments like viscometers.

54
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

C. Quality control of Finished product Cont….

3. Performance Cont….
• Particle size determination:
Cascade Impactor: Stream of particles projected
through a series of nozzles and glass slides, larger
particles are impacted first on lower velocity stage
and smaller particles are collected at higher velocity
stage.
Light Scattering Decay: As aerosol particles settle
under turbulent conditions, the change in the light
intensity of a Tyndall beam is measured.
55
 Quality control test/Quality Evaluation of MDI (aerosols) Cont…

C. Quality control of Finished product Cont….

Leak test: It is done to identify any possible leakage in the container or valve assembly. It is done by
immersing the containers in water bath at high temperature.

4. Biologic Characteristics:
• Therapeutic activity: To ensure that the drug is clinically active when inhaled or applied topically.
• Toxicity: To ensure the safety of the formulation ingredients including propellants (irritability,
chilling effects etc.)

56
 Dry powder inhaler (DPI)

In dry powder inhaler (DPI) systems, drug is inhaled as a cloud of fine particles. The drug is either
preloaded in an inhalation device or filled into hard gelatin capsules or foil blister discs which are loaded
into a device prior to use.

57
 Formulating dry powder inhalers

To produce particles of a suitable size preferably less than 5 μm, drug powders are usually micronized.
Alternatives are spray drying, spray freeze drying and supercritical fluid technology. The high-energy
powders produced by micronization have poor flow properties because of their static, cohesive and
adhesive nature. To improve their flow properties, drug particles are generally mixed with larger ‘carrier’
particles usually of 30–150 μm size of an inert excipient, usually α-lactose monohydrate. Drug and carrier
particles are mixed to produce an ordered mix in which the small drug particles attach to the surface of the
larger carrier particles.

58
 Types of DPI device

1. Unit dose devices with drug in hard gelatin capsules: In this device, each dose contained in a hard
gelatin capsule, was placed individually into the device, in a loose- fitting rotor. When patient push the
button, capsule is broken by external force by the action of installed twist or pins. Powder is released
and inhaled by patient. Example includes Spinhaler, HandiHaler, Aerolizer, Cyclohaler etc.

59
 Types of DPI device Cont….

2. Multidose devices with drug in foil blisters: The blister based DPIs have a ring of aluminum blister
inside the DPI device. Each blister contains the dose of powder drug. Dose is indicated by a dose
counter installed in DPI. When the blister is burst by applying external force then the drug powder is
inhaled by air stream when patient takes the breath. Example includes Diskhaler, Accuhaler, Diskus etc.

60
 Types of DPI device Cont….

3. Multidose devices with drug in a reservoir: In this device a dose is accurately measured and
delivered from a drug reservoir. For example, in Clickhaler, DPI a drug–lactose blend is stored in a
reservoir. Metering cups are filled by gravity from this reservoir and delivered to an inhalation passage,
from which the dose is inhaled. The device is shaken before use. The device is capable of holding up to
200 doses and incorporates a dose counter which indicates the number of metered doses. After the final
dose has been dispensed, the push button locks to prevent further use.

61
How to use a dry-powder inhaler

62
 Overview of some Inhalers Currently available on the Market
Sl. No. DPI DPI type Formulation storage Reusable Company
1 Spinhaler Single dose Capsule Yes Aventis
2 Rotahaler/DPhaler Single dose Capsule Yes GSK/Cipla
3 Cyclohaler/Aerolizer Single dose Capsule Yes Pharmachemie/Novartis
4 Handihaler Single dose Capsule Yes Boehringer-Ingelheim
5 Aerohaler Single dose Capsule Yes Boehringer-Ingelheim
6 Turbospin Single dose Capsule Yes PH&T
7 Diskhaler Multi-unit dose Blister pack Yes GSK
8 Diskus Multi-unit dose Blister strip No GSK
9 Novolizer Multidose Cartridge Yes MEDA
10 MAGhaler/Jethaler Multidose Ring tablet No Ratiopharm
11 Turbuhaler Multidose Reservoir No Astra Zeneca
12 Easyhaler Multidose Reservoir No Orion
13 Pulvinal Multidose Reservoir No Chiesi
14 Taifun Multidose Reservoir No LAB Pharma
15 Clickhaler Multidose Reservoir No Recipharm
16 Flexhaler Multidose Reservoir No AstraZeneca
17 Twisthaler Multidose Reservoir No Merck
63
 Nebulizer

A nebulizer is a drug delivery device used to

administer medication in the form of a mist
inhaled into the lungs. Nebulizers are commonly
used for the treatment of asthma, cystic fibrosis,
COPD and other respiratory diseases or
disorders. They use oxygen, compressed air or
ultrasonic power to break up solutions and
suspensions into small aerosol droplets that are
inhaled from the mouthpiece of the device.

64
 Advantage of Nebulizer over pMDI and DPI

Nebulizers deliver relatively large volumes of drug solutions and suspensions and are frequently used for
drugs that cannot be conveniently formulated into pMDIs or DPIs, or where the therapeutic dose is too
large for delivery with these alternative systems. Nebulizers also have the advantage over pMDI and DPI
systems in that drug may be inhaled during normal tidal breathing through a mouthpiece or facemask,
and thus they are useful for patients such as children, the elderly and patients with arthritis, who
experience difculties with pMDIs.

65
 Types of nebulizer

There are three categories of commercially available nebulizer –

1. Air jet Nebulizer
2. Ultrasonic Nebulizer
3. Mesh nebulizers

Air jet Nebulizer

66
 Types of nebulizer Cont…

1. Air jet Nebulizer: Jet nebulizers also called air-jet or air-

blast nebulizers use compressed gas (air or oxygen) from a
compressed gas cylinder, hospital air-line or electrical
compressor to convert a liquid (usually an aqueous
solution) into a spray. Compressed gas passes through a
Venturi nozzle typically 0.3–0.7 mm in diameter, where an
area of negative pressure is created. Liquid is drawn up a
feed tube and is fragmented into droplets. Small droplets
are carried away in the inhaled air stream and the large
droplets impact on baffles or the walls of the nebulizer
chamber and are recycled into the reservoir fluid.

67
 Types of nebulizer Cont…

2. Ultrasonic Nebulizer: Ultrasound waves are formed in

an ultrasonic nebulizer chamber by a ceramic
piezoelectric crystal that vibrate when electrically excited.
This vibrating element is in contact with a liquid reservoir
which contains the drug and its high frequency vibration
is sufficient to produce an aerosol cloud at the solution
surface.
Ultrasonic nebulisers are characterised by fast
nebulisation of medicine particles into extra small size for
enhanced absorption in the very depth of the respiratory
system, helping to increase the effects of medication.

68
 Types of nebulizer Cont…

3. Mesh nebulizers: In mesh

nebulizers aerosols are
generated by passing liquids
through a vibrating mesh or
plate with multiple apertures.
In this technology a
mesh/membrane with 1000-
7000 laser drilled holes
vibrates at the top of the liquid
reservoir, and thereby
pressures out a mist of very
fine droplets through the 69
Thank You
Very Much

70