Nanotechnology Comprises technological developments on the nanometer scale, usually 0.1 to 1000 nm.

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NANOEMULSION
Department of Pharmacy (Pharmaceutics) | Sagar savale
Mr. Sagar Kishor savale
Department of Pharmaceutics
avengersagar16@gmail.com
2015-2016

2. Content
Introduction
Classification
Defination and synonyms
Structure of Nanoemulsion
Physical properties of a Nanoemulsion
Methods of preparation
Components of Nanoemulsion
Evaluation of Nanoemulsion
Application
Conclusion
References
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3. Nanotechnology
Comprises technological developments on the nanometer scale,
usually 0.1 to 1000 nm.
The pharmaceuticals developed on the
basis of nanotechnology are termed as
‘NANOPHARMACEUTICALS’.
Introduction

4. Emulsion:
“They are thermodynamically unstable
system consisting of atleast two immissible liquid
phase, one of which is dispersed as a globules in
the other liquid phase which is continuous phase.”
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5. CLASSIFICATION :
It is based upon the nature of Dispersion Phase,
1. Oil-in-water Emulsion(o/w) (0.1-100 µm)
2. Water-in-oil Emulsion (w/o) (0.1-100 µm)
3.Micro Emulsion (0.01 µm)
4.Nano Emulsion (0.1-0.5 µm)
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6. The various nanopharmaceuticals
currently being used :
Nanoemulsion
Nanosuspension
Nanospheres
Nanoshells
 Nanocapsules
Lipid Nanoparticle
Dendrimers
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7. Nanoemulsion
•“Nanoemulsion can be defined as a oil in water(o/w)
emulsion with mean droplet daimeters ranging from
50 to 1000nm.Usually the average droplet size is
between 100-500nm.”
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Synonyms
Sub micron size emulsion
Mini emulsion
Ultrafine Emulsion

8. • transparent or translucent O/W or W/O emulsion
• droplet diameters ranging from 50-1000 nm.
[avg droplet size is between 100-500 nm]
• kinetically stable unlike microemulsions which are
thermodynamically stable
• Nanoparticles can exist core of particle
w/o form water
o/w form oil
• Ostwald ripening is the primary instability process :
Can be reduced by the addition of a second less soluble oil phase
and/or
addition of a strongly adsorbed and water insoluble polymeric surfactant.

9. Single nanoparticle
Nanoemulsion: Lipid
monolayer enclosing a liquid
lipid core.
Liposome: Lipid bilayer
enclosing an aqueous core.

10. Structure of Nanoemulsion
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Fig-1 Fig-2
Fig-3

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Types of Nanoemulsion

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13. Physical Properties of Nanoemulsion
The relative transparency of nanoemulsion.
Their response to mechanical shear or ‘rheology’.
The enhanced shelf stability of
nanoemulsion against gravitationally driven
creaming.
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14. A nanoemulsion (a) and A macroemulsion
(b) with droplet diameters of less than 100
nm and more than 1000 nm, respectively.
Nanoemulsion and Macroemulsion
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15. Difference between Emulsion and
Nanoemulsion
Themodynamically unstable.
Millky appearance.
Droplet upto few micrometer.
Thermodynamically stable.
Transluscent,isotropic.
Droplet 0.1-0.5 µm.
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Emulsion Nanoemulsion

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SMEDDS SNEDDS
It is Self-Micro emulsifying drug delivery
system
It is Self Nano emulsifying drug delivery
system
It is turbid in nature It is transparent in nature
Large amount of energy is required for
preparation as compare to nanoemulsion
Less energy required for preparation
Droplet size is 100-300nm Droplet size is less than 100nm
It is thermodynamically stable It is thermodynamically and kinetically
stable
It is optimized by ternary phase diagram It is optimized by Psedoternary phase
diagram
Difference between SMEDDS And SNEDDS

17. Advantages Of Nanoemulsions
1.Reduction of globules as the potential to:
Increase surface area
Enhance solubility
Increase oral bioavailability
More rapid onset of therapeutic action
Decrease the dose needed
2. They do not show the problems of inherent creaming,
flocculation, coalescence and sedimentation.
3.They are non-toxic, non-irritant hence can be easily
applied to skin and mucous membranes.
4. They can be taken by enteric route becoz they are
formulated with surfactants, which are approved for
human consumption (GRAS),

18. Limitations of Nanoemulsion
The manufacturing of Nanoemulsion is an
expensive process.
Stability of Nanoemulsion is a unacceptable and
creates a big problem during the storage of
formulation for the longer period time.
Less availability of surfactant and cosurfactant
required for the manufacturing of nanoemulsion.
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19. Preparation of Nanoemulsion
 Drug
poorly water soluble drug
eg: CBZ, Diclofenac, Ramipril
 Oil phase
eg: dimethicone oil , castor oil , Soyabean oil
 Aqueous phase
 Surfactant
Cremphore, lecithin
 Cosurfactant : Propylene glycol, polysorbate 80,
cetylphosphate, hydrogenated caster oil

20. Representative pseudoternary phase diagram of
surfactant and cosurfactant (Smix) mixture
showing oil/water nanoemulsion area (shaded
area)

21. Thermodynamic Studies
Prepare number of formulations
Formulations centrifuged for specific period.
select stable formulation
kept under heating and cooling cycle.
select stable formulation
subjected to a freeze-thaw cycle test
select stable formulation for further mfg

22. Methods Of Preparation Of Nanoemulsions:
High-Energy
•1. High pressure homogenization
•2 Microfludization
•3 Ultrasound energy
Undesirable for labile
drugs and macromolecules
(proteins and nucleic acids)
(for lab & industrial preparation)
Low-Energy
1. Spontaneous
2. Solvent-diffusion
3. Phase inversion temperature (PIT)
a. Rapid cooling of selected ME state
b. Dilution with water
(for lab preparation)

23. 1.High-Pressure Homogenization
In a high-pressure homogenizer, the
dispersion of two liquids (oily
phase and aqueous phase) is
achieved by forcing their mixture
through a small inlet orifice at very
high pressure (500 to 5000 psi),
which subjects the product to
intense turbulence and hydraulic
shear resulting in extremely fine
particles of emulsion.

24. Dia: High-Pressure Homogenization
Advantage: produce nanoemulsions of extremely low particle size
(up to 1nm).
Disadvantage: high energy consumption and increase in temperature
of emulsion during processing.

25. 2.Microfluidization
patented mixing technology,
use of a device called microfluidizer.
This device uses a high-pressure
positive displacement pump (500 to
20000psi), which forces the product
through the interaction chamber,
which consists of small channels
called ‘microchannels’.
The product flows through the
microchannels on to an
impingement area resulting in very
fine particles of sub-micron range.

26. Coarse emulsion The two solutions
(aqueous phase and
oily phase) are
combined together
Interaction
chamber Microfluidizer
Filtrations
desired particle size
Stable & uniform nanoemulsion.

28. Lab scale preparation:
High shearing Energy

29. Solvent evaporation method
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30. Phase inversion method
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31. Stability of Nanoemulsion
•Brownian movement
•Low rate of sedimentation – due to the small
particle size low gravitational force
•As particles become smaller, the attractive force
of van der waals will be smaller.
•High Zeta potential- more electrostatic repulsive
forces ;resulted in reducing the coalescence or
coagulation of emulsion droplets
•Optimum Thermodynamically stability ;but high
kinetic stability

32. Evaluation Of Nanoemulsion

33. Evaluation parameters of
Nanoemulsion
A) Average Globule Size And Size Distribution:-
Method used are-a)Transmission electon
Mcroscopy.
b)Droplet size analysis.
c)Light scattering.
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B) Rheological Evaluation :-
 2 major parameters : -Viscosity.
-Refractive Index.

34. C) Zeta Potential : -It is used to determine surface
charge by the help of mobility & electrophoretic
velocity of dispersed globules.
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D)Area Of Interfaces : It can be determined by
following formula.
S = 6/d
where, S = Total area of Interface
(sq.cm)
d = Diameter of Globules (cm)
E Analytical test (UV,HPLC)
F Biological studies
G In vitro drug release

35. Transmission Electron Microscopy
• Morphology and structure of the nanoemulsion were
studied using transmission electron microscopy (TEM)
• To perform the TEM observations, a drop of the
nanoemulsion was directly deposited on the holey film grid
and observed after drying

36. e.g.: TEM positive image of
Aceclofenac nanoemulsion showing
the size of some oil droplets.
. Scanning Electron Microscopy
picture of nanoemulsion.

37. Droplet size Analysis
Determined by photon correlation spectroscopy that analyzes the fluctuations in
light scattering due to Brownian motion of the particles, using a Zetasizer 1000 HS
(Malvern Instruments)
Viscosity determination
Brookfield viscometer
Refractive Index
Abbe-type Refractometer
Zeta potential measurement
The zeta potential was measured by electrophoretic mobility using Malvern
Nanosizer/Zetasizer® nano-ZS ZEN 3600 (Malvern Instruments, USA).
Biological studies
Skin Irritation Test
Plasma-time profile

38. Applications of Nanoemulsion
Use of Nanoemulsion in cosmetics.
Antimicrobial Nanoemulsion.
Nanoemulsion as Non-toxic disinfectant cleaner.
Nanoemulsion in cell culture technology.
NE as a vehicle for Transdermal drug delivery.
NE in cancer therapy and targeted drug delivery.
Nanoemulsion in the treatment of various other disease condition
Nanoemulsion as a mucosal vaccines.
Nanoemulsion as a vehicle for a ocular delivery
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39. 1.Use Of Nanoemulsions In Cosmetics
Due to their lipophilic interior,
nanoemulsions are more
suitable for the transport of
lipophilic compounds
High skin penetration due to
small size
Body Moisturizer Nanoemulsion
Face Lotion with Vitamin Nanoemulsion
Face Cream for Night Use with Vitamin Nanoemulsion

40. 2.Antimicrobial Nanoemulsions
Antimicrobial nanoemulsions are oil-in-water droplets that range from 200-600
nm.
The nanoemulsion has a broad spectrum activity against
o-bacteria (e.g., E. coli, Salmonella, S. aureus),
o -enveloped viruses (e.g., HIV, Herpes simplex),
o-fungi (e.g., Candida, Dermatophytes),
o-spores (e.g., anthrax).
nanoemulsion particles
are fuse with lipid-
containing organisms.
Due to electrostatic attraction between the
cationic charge of the emulsion and the anionic
charge on the pathogen
active ingredient
and the energy
releases destabilize
the pathogen lipid
membrane
cell lysis and
death

42. In the case of spores

43. A unique aspect of the nanoemulsions is their selective
toxicity to microbes at concentrations that are non-irritating
to skin or mucous membrane.
The safety margin of the nanoemulsion is due to the low
level of detergent & have sufficient energy in each droplet
to destabilize the targeted microbes without damaging
healthy cells.
As a result, the nanoemulsion can achieve a level of topical
antimicrobial activity that has only been previously achieved
by systemic antibiotics.

44. Nanoemulsions as a prophylactic medication
 A human protective treatment, to protect
people exposed to bio-attack pathogens such as
Anthrax ,Hepatitis and Ebola.
 The technology has been tested on gangrene
and clostridium botulism spores and even used on
contaminated wounds to salvage limbs

45. 3.Nanoemulsions As Mucosal Vaccines
(Under Trial)
 Nanoemulsions are being used to deliver either
recombinant proteins or inactivated organisms to a
mucosal surface to produce an immune response.
nanoemulsion
causes proteins
applied to the
mucosal surface
facilitates
uptake by
antigen
presenting
cells
systemic and mucosal
immune response that
involves the production of
specific IgG and IgA
antibody as well as
cellular immunity
 The first applications, an influenza
vaccine and an HIV vaccine, can proceed
to clinical trials.

46. 4.Nanoemulsions In Cell Culture Technology
 Cell cultures are used for in vitro assays or to produce biological
compounds, such as antibodies or recombinant proteins
 it has been very difficult to supplement the media with oil-soluble
substances , only small amounts of these oil-soluble substances
(lipophilic compounds ) could be absorbed by the cells.
 Nanoemulsions are a new method for the delivery of oil-soluble
substances to mammalian cell cultures.
 These nanoemulsions are transparent and can be passed through 0.1
µm filters for sterilization.
 Nanoemulsion droplets are easily taken up by the cells.
The advantages of using nanoemulsions in cell culture technology are
· Better uptake of oil-soluble supplements in cell cultures.
· Improve growth and vitality of cultured cells.
· Allows toxicity studies of oil-soluble drugs in cell cultures

47. Nanoemulsion in cancer Therapy

48. “Anti-oxidant Synergy Formulation”(ASF) suppresses
malignancy: Nanoemulsions improve its effectiveness in culture
• ASF forces differentiation of neuroblastoma (most common solid
tumor in children)...Like neurons, if they begin to differentiate, they
no longer multiply

49. The neuroblastoma in the nude mice
Tumor
No Tumor
Control
(no treatment)
ASF
Nano-emulsion

50. Nanoemulsion delivery of
Tamoxifen
to breast cancer cell lines

51. The Effect of Tamoxifen (T) and
Nanoemulsion Preparation of Tamoxifen (NT) on Cell
Proliferation
0
20
40
60
80
100
120
140
160
CellProliferation
B Control
C Tamoxifen
D Nano-Tamoxifen
Control (no treatment)
Tamoxifen (T)
Nanoemulsion
Preparation of
Tamoxifen
Days of Culture

52. Nanoemulsion delivery of anti-
inflammatory agent Aspirin in mice

53. 0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
The Anti-inflammatory properties of Nanoemulsion
Containing Aspirin in CD-1 Mice
-61%
-25%
Aspirin
+
Nano-emulsion
Alone
AspirinControl
millimeters

54. Parenteral nanoemulsions
Carbamazepine IV injection (Under trial)
 widely used anticonvulsant drug, is a poorly soluble
drug with no parenteral treatment available for patients.
Solubility of drug increases by decreasing the particle
size upto nanometer
 treatment available for patients i.e. CBZ nanoemulsion
given by IV route

55. Oral lipid nanoemulsion of Primaquine
Primaquine is one of the most widely used antimalarial and
is the only available drug till date to combat relapsing form of
malaria especially in case of Plasmodium vivax and
Plasmodium ovale.
application of PQ in higher doses is limited by severe tissue
toxicity including hematological and GI related side effects
which are needed to be minimized.
 when incorporated into oral lipid nanoemulsion having
particle size in the range of 10–200 nm showed effective
antimalarial activity against Plasmodium infection in swiss
albino mice at a 25% lower dose level as compared to
conventional oral dose.

56. PATENTED NANOEMULSIONS
Some important patents related to nanoemulsions:
1.Patent name: Method of Preventing and Treating Microbial
Infections. Assignee: NanoBio Corporation (US) US Patent
number: 6,506,803
2. Patent name: Non-toxic Antimicrobial Compositions and Methods
of Use. Assignee: NanoBio Corporation (US) US Patent number:
6,559,189 and 6,635,676,
3. Patent name: Nanoemulsion based on phosphoric acid fatty acid
esters and its uses in the cosmetics, dermatological,
pharmaceutical, and/or ophthalmological fields. Assignee: L'Oreal
(Paris, FR) US Patent number: 6,274,150
4. Patent name: Nanoemulsion based on oxyethylenated or non-
oxyethylenated sorbitan fatty esters, and its uses in the cosmetics,
dermatological and/or ophthalmological fields. Assignee: L'Oreal
(Paris, FR) US Patent number: 6,335,022

57. 5. Patent name: Nanoemulsion based on ethylene oxide and
propylene oxide block copolymers and its uses in the cosmetics,
dermatological and/or ophthalmological fields.Assignee: L'Oreal
(Paris, FR) US Patent number: 6,464,990
6. Patent name: Nanoemulsion based on glycerol fatty esters, and
its uses in the cosmetics, dermatological and/or ophthalmological
fields. Assignee: L'Oreal (Paris, FR) US Patent number:
6,541,018
7. Patent name: Nanoemulsion based on sugar fatty esters or on
sugar fatty ethers and its uses in the cosmetics, dermatological
and/or ophthalmological fields. Assignee: L'Oreal (Paris, FR) US
Patent number: 6,689,371
8. Patent name: Transparent nanoemulsion less than 100 NM
based on fluid non-ionic amphiphilic lipids and use in cosmetic or
in dermopharmaceuticals.Assignee: L'Oreal (Paris, FR)US Patent
number: 5,753,241

58. References
• Vyas S.,Khar R., 2002, Targeted And Controlled Drug Delivery
System, 1st Edition, CBS Publication, 303-329.
• Jain N.K, 2001, Controlled And Novel Drug Delivery, 1st Edition,
CBS Publication,381-399.
• R.S.R. Murthy,Vesicular and Particulate Drug Delivery Systems,
1st Edition,Career Publication,105-140.
• Leon Lachman,Herbert A.Liberman,Joseph L.Kanig,The theory
and practice of industrial pharmacy,Varghese publishing
house,Third edition,502-545.
• Monzer Fanun,Colloids in the drug delivery,CRS press
group,221-244.
Website :
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