1. National Institute of Pharmaceutical
Education and Research (NIPER)
Hyderabad
Presented by:
Ganesh Patil
M.S. (Pharm) Pharmaceutics
Presentation on:
Nebulizers
3. Introduction
The respiratory tract is one of the oldest routes used for the administration of drugs.
Over the past decades inhalation therapy has established itself as a valuable tool in the
local therapy of pulmonary diseases such as asthma or COPD.
Currently, various drug substances are marketed as inhalation aerosol products for local
pulmonary effects and about the same number of drugs are in different stages of clinical
development.
4. Fundamental aspects
Inhaled drug delivery devices can be divided into
three main categories:
1. Nebulizers
2. Pressurized Metered-Dose Inhalers (MDIs)
3. Dry Powder Inhalers (DPIs)
A good delivery device should: Generate aerosol of
suitable size ( in the range of 0.5-5 microns)
Provide reproducible drug dosing
Protect physical and chemical stability of the
formulation Simple, convenient, inexpensive and
portable.
Nebulizer
pMDI
DPI
5. Nebulizers
Nebulizers are the oldest device for respiratory
drug delivery.
The drug is formulated in aqueous solution or
suspension, which is atomized into fine
droplets via an external nebulization source
while being used for inhalation.
Most Nebulizers use compressed air for
atomization, but some use ultrasonic energy.
Nebulizers are generally used for the treatment
of cystic fibrosis, asthma, COPD and other
respiratory diseases or disorders.
6. Ultrasonic Nebulizers Jet Nebulizers Vibrating Mesh Nebulizers
• Ultrasonic nebulizers work
on the principle that
converts electrical energy
to high-frequency
vibrations using a
transducer.
• It works on the mechanism
of utilizing the gas flow
from a compressor.
• A recent technology that
uses vibrating perforated
mesh to generate respirable
sized droplets.
• There are two categories of
ultrasonic nebulizers :
1. Standard nebulizers
2. Ultrasonic nebulizers
with water interface
• They are electronic devices
and have advantages over
both jet and ultrasonic
nebulizers.
Types of Nebulizers
7. Jet Nebulizers
It works on the mechanism of utilizing the gas flow
from a compressor.
The atomization of the formulation takes place through
a small aperture in the nebulizer through which the gas
passes.
The atomized particles are air driven to a baffle and it
consists of both small and large droplets.
The impaction caused by the baffles effects the larger
droplets and then forced onto the other side, meant to be
recycled in the liquid form inside nebulizer.
A. Additional inhaled air
B. Mouthpiece- it is meant for patient inhalation
C. Release of aerosol production through the
orifice by passing the pressurized gas through it
D. Baffle- the aerosol delivery takes place
by passing through the baffles;
E. Reservoir- it contains the suitable drug
formulation
F. Pressurized air supply through the formulation.
Advantages:
• Effective in
delivering drugs
that cannot be
delivered with
pMDIs and DPIs.
• Relatively
economical.
Disadvantages:
• Noisy to use.
• Long dosing
duration (10-15
min)
• Conventional
Jet Nebulizers
have low
output.
8. Types of Jet Nebulizers
Jet nebulizers with a corrugated
tube
• Conventional constant-output
nebulizers
• Generate continuous aerosol
during inspiration, expiration, and
breath-hold.
Jet nebulizers with a collection
bag
• A dosimetric nebulizer
• Releases aerosol only during
inhalation. Aerosols generated
during expiration are stored in the
collection bag.
Breath-enhanced jet
nebulizers
• Release more aerosol during
inhalation through one-way
valves in the mouthpiece.
Breath-actuated jet nebulizers
• Sense the patient’s inspiratory
flow and deliver aerosol only on
inspiration.
9. Ultrasonic Nebulizers
Ultrasonic nebulizers are mostly preferred for aerosol
therapy.
High frequency ultrasonic waves are generated by the
vibration of a piezo-electric crystal.
The vibration mechanism gets transferred to the liquid
formulation which further produce a fountain of liquid-
drug consisting of smaller and the larger droplets.
The larger droplets are recovered into the liquid drug
reservoir. The smaller droplets are stored inside the
chamber of the nebulizer which is inhaled by the patient. A. Generator- it is responsible for the generation of
ultrasonic waves
B. Ultrasonic waves- they are generated through
the generator
C. Nozzle- aerosol mist is generated through the
nozzle
D. Ventilator
E. Mouthpiece- it is meant for inhalation
F. Power cable- it is necessary for power supply.
Advantages:
• Compact and
Silent.
• Shorter Dosing
time.
• No leakage of
aerosol.
Disadvantages:
• Heat generation due
to piezo-electric
transducer.
• Does not nebulize
viscous solutions.
• Expensive and bulky.
10. Mesh Nebulizers
Mesh Nebulizers use a vibrating plate with multiple
apertures to generate droplets.
During operation, upward and downward movement
of the aperture plate creates a micro-pumping action
that extrudes liquid through the apertures to form
liquid jets.
Each jet continues to be intact to a certain length and
then breaks to droplets.
They are electronic devices, operated by battery.
Advantages: • Can deliver liquids as well as
suspensions.
• Fast treatment time
• Reduced drug wastage
• Convenient and energy efficient
Disadvantages: • High cost.
• Clog of tiny holes of mesh.
11. Formulation
Nebulizers are aqueous-based oral inhalation solutions and suspension that must be sterile, and
are typically packaged in single-use containers (usually 1–3 ml).
S.No. Constituent Role Examples
1. Solvent To dissolve/disperse the drug and other
excipients
Sterile water
2. Co-solvent To aid solubility Alcohol, PEG
3. Tonicity Adjusters to maintain tonicity Sodium Chloride, Dextrose
4. Surfactants to aid dispersion or dissolution of the
drugs
Enhance suspension stability
Polysorbates
Sorbitanes
5. Preservatives to ensure long-term conservation of the
products.
methylparabens
propylparabens
6. Chelating Agent to enhance chemical stability EDTA
7. pH adjusters To maintain the pH Hydrochloric acid
Sodium Hydroxide
12. Marketed Formulations
S.No. Types of Marketed
Product
Drug Aerosol Device
1. AKITA Tobramycin Vibrating Mesh
2. Apixneb Tobramycin Nebulizer
3. CompAIR Iloprost Jet Nebulizer
4. MicroAir NE-U22 Budesonide Vibrating Mesh Nebulizer
5. Side Stream Plus Salbutamol Breath enhanced Jet Nebulizer
AKITA Apixneb CompAIR MicroAir NE-U22 Side Stream Plus
13. Conclusion
0
02
03
• Use of nebulizers for respiratory drug delivery is widespread in hospital and domiciliary settings.
• Nebulizers can continuously deliver drugs for a long dosing duration, thus are suitable for large
dose drugs, such as antibiotics.
• Nebulizers are not typically used for chronic-disease management because they are larger and
less convenient than pMDIs and DPIs.
• As new and emerging technologies continue to expand applications of nebulizers in respiratory
drug delivery, nebulization is expected to remain a relevant option for delivery of inhaled
medications for years to come.
14. References
• Gabrielle Pilcer, Karim Amighi, ‘Formulation strategy and use of excipients in pulmonary drug delivery’,
International Journal of Pharmaceutics, Elsevier, 2010.
• Chandel A, Goyal AK, Ghosh G, Rath G. Recent advances in aerosolised drug delivery. Biomedicine &
Pharmacotherapy. 2019 Apr 1;112:108601.
• Pritchard JN. Nebulized drug delivery in respiratory medicine: what does the future hold?. Therapeutic Delivery.
2017 Jun;8(6):391-9.
• Prajapati S, Saha S, Shambulingappa B, Ch DK, Sahoo B. Nebulizer–In vitro Bioequivalence testing
requirements: A review. Asian Journal of Pharmaceutical Research and Development. 2020;8(1):78-81.
• Hou S, Wu J, Li X, Shu H. Practical, regulatory and clinical considerations for development of inhalation drug
products. Asian journal of pharmaceutical sciences. 2015 Dec 1;10(6):490-500.
• Martin AR, Finlay WH. Nebulizers for drug delivery to the lungs. Expert opinion on drug delivery. 2015 Jun
3;12(6):889-900.
• Ari A. Jet, ultrasonic, and mesh nebulizers: an evaluation of nebulizers for better clinical outcomes.
