2. Content
Definition
Introduction
Colloidal systems
Formulation additives
Commercial NEs Formulations
Advantages
Methods of preparation
Techniques of preparation
High -pressure homogenization
Microfluidization
Phase inversion temperature technique
Titration method
Characterisation of microemulsion
Applications of nanoemulsion
conclusion
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3. Abbreviations
NE- nanoemulsion
SME-sub-micron emulsion
o/w- oil in water
w/o- water in oil
PCMX –parachlorometaxylenol
TEWL- trans epidermal water loss
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4. Definition
Nanoemulsions can be defined as oil-in-water
(o/w) emulsions with mean droplet diameters
ranging from 50 to 1000 nm.
Synonyms: sub-micron emulsion and mini-
emulsion.
Usually SMEs contain 10 to 20 per cent oil
stabilized with 0.5 to 2 per cent egg or
soyabean lecithin.
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5. Introduction
NEs are a group of dispersed particles used
for pharmaceutical and biomedical aids and
vehicles that show great promise for the
future of cosmetics, diagnostics, drug
therapies, and biotechnologies
Due to their small droplet size NEs possess
stability against sedimentation or creaming
with Ostwald ripening forming the main
mechanism of NE breakdown.
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6. • Internal structures depend on relative component
amounts, concentrations and other characteristics.
• The relative oil and water domains that form in
nanoemulsion systems are usually so small (about
10-20 nm or less in diameter) that they do not
scatter light.
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7. Nanoemulsion: Lipid Liposome: Lipid
monolayer enclosing bilayer enclosing an
a liquid lipid core. aqueous core.
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8. Nanoemulsion versus a
Microemulsion
Microemulsion Nanoemulsion
•Thermodynamically stable. •Kinetically stable
•Comparatively long term stability •Do not possess long-term stability
•Higher surfactant concentration •Requires a lower surfactant
concentration for its formation
•Less expensive then •Nanoemulsions are generally
nanoemulsion expensive
MJayne Lawrence and Warankanga Warisnoicharoen, Recent Advances in Microemulsions as Drug Delivery Vehicles (p-125),
Nanoparticle as Drug Carriers, 2006 by Imperial College Press 8
9. Nanoemulsions are transparent and slightly
opalescent.
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12. Advantages
NEs have a much higher surface area and
free energy than macro emulsions that make
them an effective transport system.
NEs do not show the problems of inherent
creaming, flocculation, coalescence, and
sedimentation, which are commonly
associated with macroemulsions.
NEs can be formulated in variety of
formulations such as
foams, creams, liquids, and sprays.
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13. Advantages
NEs are non-toxic and non-irritant, hence
can be easily applied to skin and mucous
membranes.
Since NEs are formulated with surfactants,
which are approved for human consumption
(GRAS), they can be taken by enteric route.
NEs do not damage healthy human and
animal cells, hence are suitable for human
and veterinary therapeutic purposes.
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14. Significance Small droplet size
large interfacial area
of smaller
droplet
Size. Rapid drug release
Increased bioavailability
Reduction in dose
Better profiles of drug absorption
Protection of drug(s) from the hostile
environment of the body
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15. Techniques of preparation
a. High -pressure homogenization
b. Micro fluidization
c. Phase inversion temperature technique.
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16. High -pressure homogenization
This technique
makes use of
high-pressure
homogenizer/pi
ston
homogenizer to
produce NEs of
extremely low
particle size (up
to 1nm)
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17. MICROFLUIDIZATION:
It involves the use of device that is micro fluidizer
It uses high-pressure positive displacement
pump of (500-20000)psi, which forces the
product through the interaction chamber, which
consists of small channels called “micro
channels”.
The product flows through the micro channels
on to an impingement area resulting in very fine
particles of submicron range. The two solutions
(aq. Phase and oily phase) are combined
together and processed to obtain a stable
nanoemulsion.
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22. Thermodynamic Stability
Studies
To overcome the problem of metastable
formulation
Selected formulations were centrifuged at 3500
rpm for 30 minutes
Heating and cooling cycle
Six cycles between refrigerator temperatures of
4°C and 45°C for 48 hours were done
Freeze-thaw cycle test done for the formulations
between –21°C and +25°C.
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23. Droplet Size Analysis
droplet size of the nanoemulsion is determined
by photon correlation spectroscopy
The formulation (0.1 mL) is dispersed in 50 mL
of water
Gently mix by inverting the flask.
Measurement is done using a Zetasizer 1000
HS.
Light scattering is monitored at 25°C at a 90°
angle
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24. Transmission Electron
Microscopy
The morphology and structure of the
nanoemulsion
the nanoemulsion formulation is diluted with
water (1/100).
A drop of the diluted nanoemulsion is directly
deposited on the holey film grid and observed
after drying
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25. Viscosity Determination
The viscosity of the formulations (0.5 g) can
be determined without dilution using a
Brookfield DV III ultra V6.0 RV cone and plate
rheometer at 25 ± 0.5°C.
one software used for the viscosity
calculations is Rheocalc V2.6.
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26. Applications of
Nanoemulsions
Use of nanoemulsions in cosmetics
Antimicrobial nanoemulsions
Prophylactic in bio-terrorism attack
Nanoemulsions as a mucosal vaccines
Nanoemulsion as non-toxic disinfectant
cleaner
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27. Applications of
Nanoemulsions
Nanoemulsion in the treatment of
various other disease conditions
Nanoemulsion formulations for
improved oral delivery of poorly
soluble drugs
Nanoemulsions as a vehicle for
transdermal delivery
Self-nanoemulsifying drug delivery
systems
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28. Applications of
Nanoemulsions
Nanoemulsions in cell culture technology
Nanoemulsion in cancer therapy and in
targeted drug delivery
Solid self-nanoemulsifying delivery
systems as a platform technology for
formulation of poorly soluble drugs
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29. Nanoemulsion as non-toxic
disinfectant cleaner
The disinfectant formulation is made up of
nanospheres of oil droplets #106 mm that are
suspended in water to create a NE requiring only
miniscule amounts of the active ingredient, PCMX
(parachlorometaxylenol).
The nanospheres carry surface charges that
efficiently penetrate the surface charges on
microorganisms' membranes-much like breaking
through an electric fence.
Rather than "drowning" cells, the formulation allows
PCMX to target and penetrate cell walls.
As a result, PCMX is effective at concentration levels
1-2 orders of magnitude lower than those of other
disinfectants; hence, there are no toxic effects on
humans, animals, or the environment.
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30. Nanoemulsions as a mucosal
vaccines
Used to deliver either recombinant proteins or
inactivated organisms to a mucosal surface to
produce an immune response.
An influenza vaccine and an HIV vaccine, can
proceed to clinical trials.
The NE causes proteins applied to the
mucosal surface to be adjunted and it
facilitates uptake by antigen-presenting cells.
This results in a significant systemic and
mucosal immune response that involves the
production of specific IgG and IgA antibody as
well as cellular immunity.
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31. Antimicrobial
nanoemulsions
The NE has a broad-spectrum activity against
bacteria (e.g. E. coil, Salmonella, S.
aureus), enveloped viruses (e.g. HIV, Herpes
simplex), fungi (e.g.
Candida, Dermatophytes), and spores (e.g.
anthrax).
The NE particles are thermodynamically
driven to fuse with lipid-containing organisms.
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33. Use of nanoemulsions in
cosmetics
NEs support the skin penetration of active ingredients
and thus increase their concentration in the skin.
Another advantage is the small-sized droplet with its
high surface area allowing effective transport of the
API to the skin.
Have own bioactive effects. This may reduce the trans-
epidermal water loss, indicating that the barrier
function of the skin is strengthened.
NEs are acceptable in cosmetics because there are no
inherent creaming, sedimentation, flocculation, or
coalescence that are observed with macroemulsions.
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34. Fluorine-containing
nanoemulsions for MRI cell
tracking
•cells of interest are labeled in culture using a perfluorocarbon nanoemulsion
•Labeled cells are introduced into a subject and tracked using 19F MRI or NMR
spectroscopy
•widely applied to studies of inflammation, cellular regenerative medicine, and
immunotherapy.
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35. Nanoemulsions as a vehicle for
transdermal delivery
Low systemic absorption
Site-specificity and increased drug
levels at injured tissues
Reduced toxicity
Improved pharmacological activity
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36. Parenteral Delivery
In order to increase the solubility of the drug,
To reduce drug toxicity,
To reduce hypersensitivity,
To reduce pain upon injection,
Formulated as long circulating vehicles,
Control the release rate,
As drug targeting agents,
Alternative formulation to long circulating vesicles,
On the basis of their small size avoiding uptake by the RES,
Their stability and their ease of preparation.
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37. How the top 10 big pharmaceutical companies rank in terms
of number of nano-related patents.
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39. Conclusion
NE formulations offer several advantages for the delivery of
drugs, biologicals, or diagnostic agents.
Several other products for drug delivery applications such as
Diprivan® (propofol, astra zeneca) and Ropion® (flurbiprofen)
have also reached the marketplace.
NEs are chiefly seen as vehicles for administering aqueous
insoluble drugs, as colloidal carriers for targeted delivery of
various anticancer drugs, photosensitizers, neutron capture
therapy agents, or diagnostic agents.
Because of their submicron size, they can be easily targeted
to the tumor area.
Research with perflurochemical NEs has shown promising
results for the treatment of cancer in conjugation with other
treatment modalities and targeted delivery to the
neovasculature. It is expected that further research and
development work will be carried out in the near future for
clinical realization of these targeted delivery vehicles.
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51. References:
1. Jia Xi, Qi Chang, Chak K. Chan et al, Formulation
Development and Bioavailability Evaluation of a Self-
Nanoemulsified Drug Delivery System of Oleanolic Acid.
AAPS PharmSciTech, Vol. 10, No. 1, March 2009 (#
2009).
2. Nicolas Anton & Thierry F. Nano-emulsions and Micro-
emulsions: Clarifications of the CriticalDifferences
www.springerlink.com/index/J4880Q76V1374601.pdf.
3. Shah P, Bhalodia D, Shelat P. Nanoemulsion: A
pharmaceutical review. Syst Rev Pharm [serial online]
2010 [cited 2011 Mar 16];1:24-32. Available
from: http://www.sysrevpharm.org/text.asp?2010/1/1/24/5
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