NANOPARTIKEL

Apt. Dewi Fitriani P, M.Pharm.Sci

Because of the comparable size of the
components in the human cells,
nanoparticles are of great interest in drug
delivery.

If one has to go hand in hand with nature

in treating the diseases one needs to use
the same scale

“One cannot use a human arm to massage

the hurt leg of an ant”
 content
• Terms
• Introduction • Marketed
• Ternary phase diagram preparation
• Formulation aspects • Conclusion
• Mechanism • Bibliography
• Advantage and • Questions
disadvantages
• Evaluation criteria
• Factors affecting SEDDS
• Biopharmaceutical
aspects
• Emulsion
TERMS
• Micro emulsion, nanoemulsion
• SEDDS, SMEDDS, SNEDDS , S-SEDDS
• BCS class II (Poor solubility)
• HLB
• Surfactant
• Co-surfactant and co-solvent
 INTRODUCTION
EMULSIONS
An emulsion is a dispersion in which the
dispersed phase is composed of small
globules of a liquid distributed throughout a
vehicle in which it is immiscible

Emulsification enables the pharmacist to

prepare relatively stable and homogeneous
mixtures of two immiscible liquids.
For orally administered emulsions,the o/w type permits
palatable administration of an otherwise distasteful oil by
dispersing it in a sweetened, flavored aqueous vehicle.

The reduced particle size of the oil globules may render

the oil more digestible and more readily absorbed, or if that
is not the intent, more effective in its task, as for example,
the increased efficacy of mineral oil as a cathartic when
emulsified.
EMULSIFIKASI
ADALAH PROSES PEMBENTUKAN EMULSI DARI
BAHAN-BAHAN YANG TIDAK SALING
BERCAMPUR

PRINSIP : UNTUK MEDISPERSIKAN FASE

TERDISERSI KE DALAM MEDIUM DAN
MEMBENTUK CAMPURAN YANG STABIL DAN
HOMOGEN
Nano/Microemulsions, SNEDDS and SMEDDS
• In the pharmaceutical world a distinction has been made
between SEDDS and SMEDDS, on the basis that the
latter are visibly transparent.

• The basic difference between SEDDS also called as self

emulsifying oil formulation (SEOF). SMEDDS is SEDDS
typically produce micro emulsions with a droplet size
between 100 and 300 nm while SNEDDS form
transparent nano emulsions with a droplet size of less
than 50 nm.
• The visual clarity of an emulsion of 50nm particles may
offer a Marketing advantage, particularly if the
emulsification takes place ex vivo.
• SEDDS or self-emulsifying oil formulations (SEOF) are
defined as Isotropic mixtures of natural or synthetic oils,
solid or liquid surfactants or, alternatively, one or more
hydrophilic solvents and co-solvents/ surfactants.

• Self-emulsification is a term used to describe

emulsification which occurs with little or no input of
energy. The process may be spontaneous or may require
low levels of shear – but will contrast with
Conventional Emulsification which requires high
shear.
• These systems form fine oil-in-water (o/w) emulsions or
micro emulsions (SMEDDS)upon Mild agitation
followed by dilution in aqueous media, such as
gastrointestinal (GI) fluids.
NANOEMULSION
 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
 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.
 Nes=Nanoemulsions
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
• 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.
Nanoemulsion: Lipid
monolayer enclosing
a liquid lipid core.
 Nanoemulsion versus
Macroemulsion
Macroemulsion Nanoemulsion
•Kinetically stable •Thermodynamically stable.

•Do not possess long-term stability •Comparatively long term stability

•Requires a lower surfactant •Higher surfactant concentration

concentration for its formation

•Less expensive then •Nanoemulsions are generally

nanoemulsion expensive
• Nanoemulsions are transparent and slightly
opalescent.
Formulation additives
A Typical Formulation
 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.
 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.
Significance
Small droplet size
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
 Techniques of preparation
a. High -pressure homogenization

b. Micro fluidization

c. Phase inversion temperature

technique.
High -pressure homogenization
• This technique
makes use of
high-pressure
homogenizer/pist
on homogenizer
to produce NEs of
extremely low
particle size (up
to 1nm) 
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.
 Characterization of Nanoemulsion

• transmission electron microscopy,

• % Transmitance
• NE droplet size analysis,
• Polidispersity index
• viscosity determination,
• Zeta potential
• in vitro skin permeation studies,
 Characterization of Nanoemulsion

• skin irritation test, 

• in vivo efficacy study,
• thermodynamic stability studies
 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.
 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
 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 
a. Transmition Electron
Microscope(TEM)
b.Scanning Electron
Microscop(SEM)
 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.
    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 

 
    Applications of Nanoemulsions

• Nanoemulsion formulations for

improved oral delivery of poorly
soluble drugs 
• Nanoemulsions as a vehicle for
transdermal delivery 
• Self-nanoemulsifying drug delivery
systems 
    Applications of Nanoemulsions

• Nanoemulsions in cell culture technology

• Nanoemulsion in cancer therapy and in

targeted drug delivery
• Nanoemulsion in the treatment of various
other disease conditions
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.
 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.
 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.
Prophylactic in bio-terrorism attack
COSMETIC
 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.
Nanoemulsions as a vehicle for transdermal delivery 

• Low systemic absorption

• Site-specificity and increased drug
levels at injured tissues
• Reduced toxicity
• Improved pharmacological activity
 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.
Commercial NEs Formulations
 Nanosuspension
Rerata [AUC]0-4 ±
Kelompok Rerata %DAI ± SD
SD
Na-CMC 0,5% 4,55 ± 0,36 _
Placebo (tanpa obat) 4,24 ± 0,44 _
Ketoprofen dosis 2,25 3,03 ± 0,28 33,47 ± 6,05
mg/kgBB
Ketoprofen dosis 4,5 2,62 ± 0,39 42,41 ± 8,62
mg/kgBB
Ketoprofen dosis 9 2,01 ± 0,31 55,75 ± 6,72*
mg/kgBB
Nano-ketoprofen 2,25 1,91 ± 0,09 54,85 ± 2,03*
mg/kgBB
Nano-ketoprofen dosis 1,44 ± 0,22 65,90 ± 5,16
NILAI % DAYA
4,5 mg/kgBB
ANTI INFLAMASI (%DAI)
UNTUK SUSPENSI
Nano-ketoprofen dosisKETOPROFEN
9 DOSIS
0,91 ± 0,19 78,42 ± 4,56
9 MG/KG BB HAMPIR SAMA DENGAN
mg/kgBB
NILAI %DAI NANO-KETOPROFEN DOSIS
2,25 MG/KG BB
 Ternary phase diagram
• Pseudo ternary phase diagram is used to map the
optimal composition range for three key excipients
according to the resulting droplet size following self
emulsification, stability upon dilution and viscosity.
• A Titration method is employed to construct phase diagram.
• Mixture of oil with surfactant is prepared at different ratios
(e.g. 10:0, 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9, 0:10) into
different vials.
• A small amount of water in 5 % (w /w) increments is added
into the vials.
• Following each water addition the mixture in vials is
centrifuged for 2 to 3 minute and is incubated at 25 C or 48
hrs with gentle shaking.
 SEDDS
SNEDDS/SMEDDS
Formulation of SEEDS :
• Drug
• Oils
• Surfactant
• Co surfactant
• Co solvent
• Polymer
Mainly BCS classification class II drugs :

• Nifedipine, • Glibenclamide
• Cyclosporin, • Griseofulvin
• Digoxin • Haloperidol
• Steroids • Ibuprofen
• Diazepam • Phenytoin
• Carbamazepine Sodium
• FOLIC acid
 BCS

Class II Class I
Low solubility High solubility
High High
permeability permeability

Class IV Class III

Low solubility High solubility
Low Low
permeability permeability
 OILS

• Oils can solubilize the lipophilic drug in a specific

amount.
It is the most important excipient because it can facilitate
self-emulsification and increase the fraction of lipophilic
drug transported via the intestinal lymphatic system,
thereby increasing absorption from the GI tract.
• Long-chain triglyceride and medium-chain triglyceride
oils with different degrees of saturation have been used
in the design of SEDDSs.
• EG.mono-di-tri-glycerides DL-alpha-Tocopherol,
• Fractionated triglyceride of coconut oil(medium-chain
triglyceride)
• Corn oil, Olive oil, Oleic acid, Sesame oil, Hydrogenated
soya bean oil, Hydrogenated vegetable oils,Soyabean oil,
Peanut oil, Beeswax
 Surfactant
• 1: Anionic Surfactants, where the hydrophilic group carries a negative charge such
as carboxyl (RCOO-), sulphonate (RSO3 -) or sulphate (ROSO3 -).
Examples: Potassium laurate, SLS
• 2: Cationic surfactants, where the hydrophilic group carries a positive charge.
Example: quaternary ammonium halide.
• 3: Ampholytic surfactants (also called zwitterionic surfactants)
Example: sulfobetaines.
• 4: Nonionic surfactants, where the hydrophilic group carries no charge but derives
its water solubility from highly polar groups such as hydroxyl or polyoxyethylene
(OCH2CH2O).
Examples: Sorbitan esters (Spans), Polysorbate (Tween).

• Nonionic surfactants with high Hydrophilic Lipophilic Balance

(HLB) values are used in formulation of SEDDS (e.g., Tween,
Labrasol, Labrafac CM 10, Cremophore, etc.).
• 30–60% w/w is used of the formulation in order to form a stable
SEDDS. Surfactants have a high HLB(>12) and hydrophilicity,
which assists the immediate formation of o/w droplets and/or rapid
spreading of the formulation in the aqueous media
 Cosolvents/Cosurfactant
• Organic solvents, suitable for oral
administration (ethanol, propylene glycol
(PG) polyethylene glycol (PEG), etc) may
help to dissolve large amounts of either
the hydrophilic surfactant or the drug in
the lipid base and can act as co-surfactant
in the self emulsifying drug delivery
systems
 Other components
• These may be pH adjusters,
• flavors,and
• Antioxidant agents.
• Lipophilic antioxidants(E.g. alpha
tocopherol, propyl gallate,ascorbyl
palmitate ) may be required to stabilize
the oily content of SMEDDS formulation.
• Consistency builder
 Mechanism
• The process by which self-emulsification takes place is not yet well
understood.
• But ,According to ‘Reiss’ self emulsification occurs when the entropy change
that favors dispersion is greater than the energy required to increase the
surface area of the dispersion.
• The free energy of the conventional emulsion is a direct function of the
energy required to create a new surface between the oil and water phases
and can be described by the equation:
ΔG = Σ N π r2 σ
• Where,
• ΔG is the free energy associated with the process (ignoring the free energy
of mixing), N is the number of droplets of radius r and σ represents the
interfacial energy.
• In the case of self-emulsifying systems, the free energy required to form the
emulsion is either very low and positive or negative (then, the emulsification
process occurs spontaneously).
• Lesser interfacial tensionlesser free energystable emulsion
Potential Mechanism for Absorption Enhancement
 Advantages
• Improvement in oral bioavailability: Dissolution rate
dependant
Increase in specific surface  more efficient drug
transport through absorptive brush border membrane
leading to improved bioavailability. E.g. In case of
Halofantrine approximately 6-8 fold increase in
bioavailability of drug was reported in comparison to
tablet formulation.

• Ease of manufacture and scale-up:

SMEDDS require very simple and economical
manufacturing facilities like simple mixer with agitator
and volumetric liquid filling equipment for large-scale
manufacturing. This explains the interest of industry in
the SMEDDS.
• Reduction in inter-subject and intra-
subject variability and food effects:
• Ability to deliver peptides that are prone
to enzymatic hydrolysis in GI.
• No influence of lipid digestion process as
found in other LDDS.
• Increased drug loading capacity
• Protection of sensitive drug substances.
 Disadvantage
• The drawbacks of this system include chemical
instabilities of drugs and high surfactant concentrations.
• The large quantity of surfactant in self-emulsifying
formulations (30-60%) irritates GIT.
• Volatile cosolvents in the conventional self-emulsifying
formulations are known to migrate into the shells of soft
or hard gelatin capsules, resulting in the precipitation of
the lipophilic drugs.
• One of the obstacles for the development of self micro
emulsifying drug delivery systems (SMEDDS) and other
lipid-based formulations is the lack of good predicative
in vitro models for assessment of the formulation.
 Construction of phase diagram
• The resulting mixture is evaluated by visual and microscopy
observation. For phase diagram the micro emulsion is the
region of clear and isotropic solution.
• Coarse emulsion is the region of cloudy dispersion.
 Evaluation of SEDDS
STABILITY STUDIES
• 1.Heating cooling cycle: Six cycles ,(4°C) and (45°C) for 48 hrs.
• 2. Centrifugation: 21°C and 25°C with storage at ach temperature for not less than 48
h is done at 3500 rpm for 30 min.
• 3.Freeze thaw cycle

DISPERSABILITY TEST
• The efficiency of self emulsification of oral nano or micro emulsion is assessed using a
standard USP XXII dissolution apparatus 2.
• 1ml of each formulation is added to 500 ml of water at 37 ± 0.5°C. A standard stainless
steel dissolution paddle is used at 50 RPM .
• Grade A: Rapidly forming (within 1 min) nano
• emulsion having a clear or bluish appearance.
• Grade B: Rapidly forming slightly less clear having a bluish white appearance.
• Grade C: Fine milky emulsion that forms within 2 min.
• Grade D: Dull grayish white emulsion having slightly oily appearance that is slow to
emulsify.
• Grade E: Formulation exhibiting either poor or minimal emulsification with large oil
globules present on the surface.
• Grade A and Grade B formulation will remain as nanoemulsion when dispersed in
GIT. While
TURBIDIMETRIC EVALUTION
• This is done to identify efficient self emulsification by establishing whether
the dispersion reaches equilibrium rapidly and in a reproducible time.
• Nephelo turbid metric evaluation is done to monitor the growth of
emulsification.

DROPLET SIZE AND PARTICAL SIZE MEASUREMENT

Most crucial for drug release and stability
• Photon correlation spectroscopy (which analyses the fluctuations in light
scattering due to Brownian motion of the particles) which can measure
sizes between 10 and 5000 nm.

REFRACTIVE INDEX AND PERCENT TRANMISSION

• Refractive index and percent transmittance proves the transparency of
formulation
Refractometer is generally used
UV visible spectrophotometer is used for % transmittance.
ZETA POTENTIAL MEASUREMENT :
• This is used to identify the charge of the droplets.
• In conventional SMEDDS, the charge on an oil droplet is negative
due to presence of free fatty acids.

DRUG CONTENT:
• Drug content in the solvent extract of pre weighed SEDDS was
analyzed by suitable analytical method against the standard
solvent solution of drug.

IN VITRO DRUG DIFFUSION STUDY :

• It is done using a Dialysis technique.The dialyzing medium was
phosphate buffer pH 6.8.
• One end of pre-treated cellulose dialysis tubing (7 cm in length)
was tied with thread, and then 1 ml of self-emulsifying
formulation was placed in it along with 0.5 ml of dialyzing
medium.
Continuous...

• The other end of the tubing was also secured

with thread and was allowed to rotate freely in
200 ml of dialyzing medium and stirred
continuously at 100 rpm with magnetic bead on
magnetic plate at 37°C.
• The % drug diffused is measured.
 FACTORS AFFECTING SMEDDS
• 1. CONCENTRATION OF DRUG:
Drugs which are administered at very high dose are not suitable for
SMEDDS unless they exhibit extremely good solubility in at least one of
the components of SMEDDS, preferably lipophilic phase.

• 2. SOLUBILITY OF DRUG:
The ability of SMEDDS to maintain the drug in solubilised form is greatly
influenced by the solubility of the drug in oily phase.
If the surfactant and co-surfactant contribute to a greater extent for
solubilisation then there is risk of precipitation.

• 3. POLARITY OF LIPID PHASE:

The polarity of lipid phase is one of the factors that govern the release of
the drug from the micro-emulsion. HLB, chain length, degree of
unsaturation of the fatty acid, molecular weight of the hydrophilic portion
andconcentration of the emulsifier govern polarity of the droplets.
Marketed products
 Conclusion
• SEEDS substantially improved solubility/dissolution,
absorption sand bioavailability of poorly water soluble
drugs.
• As improvement or alternatives of conventional liquid
SEEDS such as S-SEDDS is superior in reducing
production cost, simplifying industrial manufacture, and
improving patient compliance and stability.
• The efficiency of the SEEDS formulation is cases-specific
in most instances; thus, composition of the SEEDS
formulation should be determined very carefully.
• Since a relatively high concentration of surfactants is
generally employed in the SEEDS formulation, toxicity
of the surfactant being used should be taken into
account.
 Bibliography
• Kyatanwar A U et al. /Self micro-emulsifying drug delivery system (SMEDDS) :
Review Journal of Pharmacy Research 2010, 3(1),75-83

• KUMAR A et al./SELF EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS):

FUTURE ASPECTS, International Journal of Pharmacy and Pharmaceutical
Sciences. Vol 2, Suppl 4, 2010

• Pathak Aet al. /Recent advances in self emulsifying drug delivery system - A
review, Drug Invention Today 2010,2(2),123-129

• Mishra N et al,/ Der Pharmacia Lettre New Strategy for Solubilization of poorly
soluble drug- SEDDS 2009, 1 (2) 60-67

• BO tang et al,/Development of solid self emulsifying drug delivery system : preparation

techniques and dosage forms, Drug discovery today,vol 13,july 2008, 13-14

• KAMBLE A V et al/ SELF MICRO EMULSIFYING DRUG DELIVERY

SYSTEM,International Journal of Pharma and Bio Sciences V1(2)2010
• Willey,J and Sons. 2013.Drug Delivery Strategies for Poorly Water-Soluble
Drugs, First Edition. Edited by Dennis Douroumis and Alfred Fahr.
RESEARCH PAPERS
 QUESTION
Write a short note on self emulsifying
drug delivery system.
 Emulgel
Emulgel is a combination of gel and emulsion
where emulsion used can be both type W/O and
O/W as a vehicle for purpose to deliver selected
drug to the skin. Water Phase containing the
gelling agent converts a classic emulsion in
emulgel .
Dermatological use of Emulgel has many
favourable properties like easy spreadable,
greaseless, being thixotropic, water-soluble,
easy removal, longer shelf life, non-staining,
and bio-friendly.
 Nanoemulgel
Formation containing Nanoemulsion in gel base are
called nanoemulgel, is the addition of Nanoemulsion
system intergraded into gel matrix which influences a
better skin permeation
SKIN Barriers
 Important Component of
Nanoemulgel
a. Oils: Oils used in Nanoemulsion are generally
mineral oils used as the vehicle for drugs E.g. castor
oils and various fixed oils (cottonseed oil, maize oils,
arachisoil ) Olive Oil, Coconut Oil, eucalyptus oil,
rose oil, clove oil etc.

b. Aqueous Phase: Commonly distilled water is used

as a aqueous phase for the preparation of Nanomulsion
and hydrogel.
c. Surfactantand Co-Surfactant: urfactants are used both
to give emulsification at the time of formulation and
control day to day stability during shelf life of prepared
Nanoemulsion. General selection of surfactant depends
on the type of emulsion .

(O/W or W/O) E.g. Span 80 (Sorbitanmonooleate), Acrysol

K 140, Polyethylene-glycol-40-stearate, Acrysol, Labrasol,
Stearic acid, PlurolOleique, Tween 80 (Polyoxyethylene-
sorbitan-monooleate), Labrafil, Sodium stearate, Where
agents like Transcutol ,Captex, Cammul, Migyol, etc. can
be use as co-surfactant or co-solvents.
d. Gelling Agent: Polymers essential to give the
structural network for the preparation of gels are
known as gelling agents E.g. Natural - Agar,
Tragacanth, Guar gum, Xanthan Gum, Semi-synthetic
and Synthetic Carbapol, Poloxamer, HPMC (cellulose
derivatives)
Methods Of Formulation
Formulation of Nanoemulsion-gel can be summarized in
to following steps,
a. Screening of components
b. Preparation of Nanoemulsion
c. Preparation of Nanoemulgel.

a. Screening of components
Drug Solubility was determined in different oils by excess
addition of drug into different components followed by
continuously stirred 72 hours to achieve equilibrium.
After that samples centrifuged and supernatant was
taken and solubility was determined by appropriate
analytical methods. Then, excipients in each category
with the highest solubility of drug are selected for further
studies
b. Preparation of Nanoemulsion: The drug is then
solubilized in oil and oil is addend in to Nmix, this mixture
is diluted with water to form of Nanoemulsion of given
drug.

c. Preparation of Nanoemulgel: Gel base is prepared using

1g of the Carbopol in a required quantity of water. After
complete swelling and dispersion of Carbopol solution
during 24 hours period, prepared Nanoemulsion is slowly
added under continues stirring. Addition of
Triethanolamine gives homogeneous gel dispersion. Finally
required remaining part is adjusted with distilled water
 Optimization And Evaluation

a. Measurement of pH : Various Topical formulations have pH in

range of 5-6 measured by using pH meter. For testing, 1g of gel is
dissolve in 10ml water. PH of each formulation is done on
triplicate to avoid error

b. Size of globules: To determine this parameter 1.0 gm of gel was

dissolved in water and stirred to get dispersion and then sample
was injected into the photocell of Malvern zetasizerr.

c. Swelling Index: 1 gm of prepared topical nanoemulgel is taken on

porous aluminium foil which is then placed on 10 ml of 0.1 N NaOH
solutions. Sample removed time to time and weight is noted till no
further change in weight:
Swelling Index (SW) % = [[Wt-Wo]/Wo]*100
Where, (SW) % = Percentage swelling,
Wo = Original weight of nanoemulgel
d. Spreadability of Gellifed Nanoemulgel:
It can be measured by using Slip and Drag basis, as
suggested by Mutimer, Here 2 gm od Nanoemulgel is
palced on lower ground slide which is fixed with wooden
block and sandwiched is prepared by other glass slide
having similar size which is attached with hook having
500mg weight placed. After 5 min extra weight was placed
on pan connected with second slide. Time to cover 5cm
distance for upper slide was noted and used to calculate
spreadability by using following equation:
Spreadability (S) = M*L / T
Where, M = Weight tied to upper slide,
L = Length of glass slides
e. Skin irritation test
0.25 gm Nanoemulgel is applied to each different site (two
sites/rabbit). After 24 hr of application rabbit skin site are wiped and
cleaned, Change in colour of skin or undesirable change in
morphology is noted and checked.

f. In-vitro Diffusion studies

Franz diffusion cell is used to perform diffusion study of prepared
nanomeulgel. A cellophane membrane is used for study and 0.5g of
sample applied on membrane and diffusion is carried out for 8 hr at
37±1°C using phosphate buffer (pH 7.4). At time interval of 1 hr, 1 ml
pg sample is collected and replaced with new buffer solution.
Collected samples are analyzed by using suitable analytical method