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Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

AENSI Journals Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page:
AENSI Journals Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page:

AENSI Journals

AENSI Journals
Advance s in Environmental Biology

Advance s in Environmental Biology



Jou rnal home page: http://www.aensiweb.com/AEB/

Jou rnal home page: http://www.aensiweb.com/AEB/

Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page: http://www.aensiweb.com/AEB/
Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page: http://www.aensiweb.com/AEB/
Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page: http://www.aensiweb.com/AEB/
Advance s in Environmental Biology ISSN-1995-0756 EISSN-1998-1066 Jou rnal home page: http://www.aensiweb.com/AEB/

a system: an overvi ew





dru g


Sarfaraz Ahmad, Md. Sajid Ali, M

d. Sarfaraz Alam,Md. Intakhab Alam, Nawazish

College of Pharmacy, Jazan University, Jaza n, Saudi Arabia.


Address For Correspondence:

Sarfaraz Ahmad, College of Pharmacy, Jaza n University, Jazan, Saudi Arabia. Pin code-45142 E-mail: sarfaraz3030@gmail.com, Mobile No: +966-551286443

This work is licensed under the Creativ e Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by /4.0/

(CC BY). http://creativecommons.org/licenses/by /4.0/ Received 28 August 2016; Accept ed 18 October 2016;

Received 28 August 2016; Accept ed 18 October 2016; Available online 22 October 2 016

Accept ed 18 October 2016; Available online 22 October 2 016 ABSTRACT Nanoemulsions (NE) are submicron


Nanoemulsions (NE) are submicron sized e mulsions that are under research as drug carriers to improve the d elivery of therapeutic agents. These arethermodynamically stable transpar ent or translucent nano-sized dispersions having the droplet size 10 –100 nm.These are stabilized

by an interfacial film of surfactant and cosur factant molecule. Several techniques are to be used for preparation

microfluidization, high pressure homogeniza tion, low energy emulsification and solvent evaporation methods and the parameters that are

droplet size analysis,viscosity determination, drug content, refracti ve index, pH, zeta potential,

Electron microscopy (TEM & SEM), therm al stability, release and in-vitro & in-vivo studies. This review foc usesin brief on current status

of nanoemulsions in the delivery of drugs an d cosmetics, formulation aspects, advantage and disadvantage of na noemulsion.

to be used for its characterization includes

of nanoemulsions including

KEYWORDS: Nanoemulsion, Physico chemical properties, Drug delivery system, Surfactant, Co-surfacta nt, Applications


Nanoemulsion (NE)is one of submicron size[1]. Nanoemulsions dispersions of oil-in-water (o/w) cosurfactant molecule having the

the most proficient dispersed nanosystems of d roplet size ranging to are thermodynamically stable transparent or t ranslucent nano-sized or water-in-oil (w/o) stabilized by an interfacial f ilm of surfactant and droplet size 10–100 nm [2]. One of the unique ch aracteristics of the NE

technology is the relatively hi gh percentage of total particle volume occup ied by the internal

hydrophobic oil core of the dro plets. Nanoemulsions are also referred to as mini-e mulsions and ultrafine emulsions. Phase behaviour studies have shown that the size of the droplets is governed by the surfactant phase

either temperature or

structure (bicontinuousmicroemuls ion or lamellar) at the inversion point induced by

composition. This provides high sol ubilization oflipophilic compound as compared tooth er lipoidal vehicle such as liposomes[3].The capacity of na noemulsions to dissolve large quantities of hydroph obics, along with their

mutual compatibility and ability to

protect the drugs from hydrolysis and enzymatic d egradation make them

ideal vehicles for the purpose of pa renteral transport[4, 5]. Further, the frequency and d osage of injections can be reduced throughout the drug the rapy period as these emulsions guarantee the release of drugs in a sustained

and controlled manner over long

periods of time. Additionally, the lack of flocculati on, sedimentation and

creaming, combined with a large su rface area and free energy, offer certain advantages o ver emulsions of larger

particle size.Their very large interf acial area positively influences the drug transport an d their delivery, along with targeting them to specific site s [6]. Reducing droplet sizes to the nanoscale leads t o some very interesting

world of nanomaterials,

nanoemulsions hold great promise

as useful dispersions of deformable nanoscale dropl ets that can have flow

physical properties, such as optical transparency and unusual elastic behavior[7]. In the

properties ranging from liquid to hi ghly solid and optical properties ranging from opaqu e to nearly transparent.


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

Moreover, it is very likely that nanoemulsions will play an increasingly important role commercially, since they can typically be formulated by using significantly less surfactant than is required for nanostructured lyotropicmicroemulsion phases [8, 9]. Nanoemulsions are part of a broad class of multiphase colloidal dispersions. Although some lyotropic liquid crystalline phases, also known as “micellar phases”, “mesophases”, and “microemulsions”, may appear to be similar to nanoemulsions in composition and nanoscale structure, such phases are actually quite different. Now-a-day’s nanoemulsions are frequently used for various purpose like delivery of vaccine, DNA encoded drug,antibiotics, cosmetic and topical preparations and can be administrated via various routes like oral, pulmonary, ocular and transdermal etc. [10]. Research works proves that nanoemulsion is far more efficient drug delivery system than other drug delivery system[11,12]. Nanoemulsions are made from surfactants approved for human consumption and common food substances that are “Generally Recognized as Safe” (GRAS) by the FDA. These emulsions are easily produced in large quantities by mixing a water-immiscible oil phase with an aqueous phase under high shear stress, or mechanical extrusion process that is available worldwide [8,13].

Classification Of Nanoemulsions [14]:

Table 1: Depending on the composition there are three types of Nano emulsions:






in Water Nanoemulsion




Oil droplets are dispersed in the continuous aqueous phase.









Water droplets are dispersed in the continuous oil phase.


Bi-Continuous Nanoemulsion

Micro domains of oil and water are inter-dispersed within the system.

In all three types of nanoemulsions, the interface is stabilized by an appropriate combinationof surfactants and/or co-surfactants. The major difference between emulsion and nanoemulsion are, Nanoemulsions are thermodynamically and kinetically stable, while emulsions are unstable. Emulsions are cloudy require the large energy input while nanoemulsions are formed either with (sometime spontaneously) or without high energy input. Emulsions have smaller surface area to volume, less free energy than nanoemulsion. Emulsions require high amount ofsurfactant as compared to nanoemulsion e.g., 20-25% surfactant is added in the preparation of emulsion but 5- 10 % surfactant is suitable for nanoemulsion[15].

but 5- 10 % surfactant is suitable for nanoemulsion[15]. Fig. 1: N. Nanoemulsion: Droplet diameter less

Fig. 1: N. Nanoemulsion: Droplet diameter less than 100 nm; M. Microemulsion: Droplet diameter more than 1000 nm

Table 2: Advantages and disadvantages of nanoemulsion[16-19]

Advantages of nanoemulsion over other dosage forms

Disadvantages of nanoemulsion based systems


Increase the rate of absorption.


Use of a large concentration of surfactant and co-


Eliminates variability in absorption.

surfactant necessary for stabilizing the nanodroplets.


Helps in solublizing lipophilic drug.


Limited solubilizing capacity for high-melting


Provides aqueous dosage form for water insoluble




The surfactant must be nontoxic for using


Increases bioavailability.

pharmaceutical applications.


Various routes like tropical, oral and intravenous can


Nanoemulsion stability is influenced by environmental

be used to deliver the product.


parameters such as temperature and pH. These parameters change upon nanoemulsion delivery to patients.


Rapid and efficient penetration of the drug moiety.


Helpful in taste masking.


The formulation of nanoemulsions is an expensive


Provides protection from hydrolysis and oxidation

process due to size reduction of droplets is very difficult as it required a special kind of instruments and process methods.







o/wnanoemulsion is not exposed to

attack by water and air.



Homogenizer (instrument required for

10. Liquid dosage form increases patient compliance.

the nanoemulsions formulation) arrangement is an expensive Moreover


11. Less amount of energy requirement.

12. Nanoemulsions are thermodynamically stable system

microfluidization and ultrasonication (manufacturing process)


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

and the stability allows self-emulsification of the system whose properties are not dependent on the process followed.

require large amount of financial support.


The stability of nanoemulsions is quite unacceptable


Same nanoemulsions can carry both lipophilic and

and produces a big problem during the storage of formulation for

hydrophilic drugs.

the longer time.


The use of nanoemulsion as delivery systems can


Ostwald ripening is the main problem associated with

improve the efficacy of a drug, allowing the total dose to be

unacceptability of nanoemulsions formulations. Ostwald ripening

reduced and thus minimizing side effects.

is due to the high rate of curvature of small droplet show greater solubility as compared to large drop with a low radius of curvature.


There is a perception in the personal care and

cosmetic industry that nanoemulsions are expensive to produce. Expensive equipments are required as well as the use of high concentrations of emulsifiers.


Lack of understanding of the mechanism of

production of submicron droplets and the role ofsurfactants

and cosurfactants.


Lack of understanding of the interfacial chemistry that

is involved in production of nanoemulsions.

Formulationof Nanoemulsion:

Nanoemulsions are multiphase colloidal dispersion which is generally characterized by its stability and clarity. There is an application of high shear obtained by micro fluid or ultrasonic approach used to reduce the droplet size to nanoscale. There is a marginal difference between the terms nanoemulsion and microemulsion. The microemulsion generally forms through thermodynamic self-assembly whereas nanoemulsion requires external shear for rupturing the droplets. In retrospect, the historical choice of the word “microemulsion” to describe the nanoscale is unfortunate since they are structurally between 1 to 100 nm as for nanoemulsion. Microemulsions are not the emulsions of micro scale droplets. They are formed by self-assembled equation phase in which the surface tension dose not play a significant role. The nanoemulsions underline the basic principle in its formulation. They generally comprises of two immiscible phase with an interfacial tension between them reduced by addition of surfactant[20].

Components of Nanoemulsion[21]:

Following are the three main components of nanoemulsions:

1. Oil

2. Surfactant/Cosurfactant

3. Aqueous phase


Solubility of the drug in the oil phase is an important factor for the selection of oils. Specially this is very important in the case of oral formulation development, since the ability of nanoemulsionto maintain the drug in solubilized form is greatly influenced by the solubility of the drug in the oil phase. If the surfactant or cosurfactant is contributing to drug solubilization, there could be a risk of precipitation, as dilution of nanoemulsion in the gastrointestinal tract will lead to lowering of the solvent capacity of the surfactant or cosurfactant (Table 3).


There arethree typesof surfactantsused for stabilizing the systems. These are anionic, cationic, and nonionic. Nonionic surfactants are relatively less toxic than their ionic counterparts and typically have lower CMCs. Also, o/w nanoemulsion dosage forms for oral or parenteral use based on nonionic surfactants are likely to offer in vivo stability. Therefore, proper selection of surfactants becomes a crucial criterion. Another important criterion is the selection of surfactant with proper HLB value. Hydrophilic surfactant and cosurfactant are considered to prefer the interface and to lower the necessary energy to form the nanoemulsions, consequently improving the stability. For example, the required HLB value to form o/w nanoemulsions should be greater than 10. The right blend of low and high HLB surfactants leads to the formation of a stable nanoemulsion upon dilution with water[22] (Table 3 & 4).


Cosurfactants are added to obtain nanoemulsion systems at low surfactant concentration. Short- to medium-chain length alcohols (C3–C8) are commonly added ascosurfactants, which further reduce the interfacial tension and increase the fluidity of the interface. They also increase the mobility of the hydrocarbon tail and allow greater penetration of the oil into this region. Alcohols may also increase the miscibility of the aqueous and oily phases due to its partitioning between these phases. Therefore, ethanol, isopropyl alcohol, 1-butanol, and propylene glycol were selected as cosurfactants. PEG 400 and Carbitol were


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130


relatively bearable.





show increased




into formulations and are

Table 3: Commonly used oils, surfactants and cosurfactants for the preparation of nanoemulsion [23].

S. No.






Captex 355 (Glyceryl Tricaorylate/Caprate)

Capryol 90


Transcutol p


Captex 200 (Propylene Dicaprylate/Dicaprate Glycol)

Tween 80


Glycerin, Ethylene glycol


Captex 8000 (Glyceryl Tricaprylate) (Tricaprylin)

Lauroglycol 90


Propylene glycol


Witepsol (90:10 % w/w c12 Glyceride tri: diesters)

PEG MW > 4000


Softigen 701, 767


Myritol 318 (c8/c10 triglycerides)







2125 CS


Isopropyl myristate (Myristic acid isopropyl ester)

Poloxamer 124




and 188

Table 4: Types of Surfactant [24-26]









Non-ionic surfactants includepolyoxyethylene surfactants such as Brij 35 (C12E35) or sugar esters such as sorbitanmonooleate (Span 80), Tween.



Cationic surfactants include lecithinpreparations from a variety of sources including soybean and egg are available commercially and contain diacylphosphatidylcholine as its major constituent. Quaternary ammonium alkyl salts form one of the best known classes of cationic surfactants.



Anionic surfactant include sodium bis-2-ethylhexylsulphosuccinate (AOT) which is twin-tailed and is a particularly effective stabiliser of w/o microemulsions. Anionic surfactant is in common use consist of soap of Alkali, Amines, Metals,Sulphated alcohal and Sulphonates Alkali Soap:Potassium and sodium stearate Amines Soap:Ethanolamine,Di ethanolamine, Isopropanolamine, oleic acid Metals Soap: Calcium and aluminum stearate



Substances whose ionic characteristics depend upon pH of the system.Phospholipidsare a notable example and exhibit excellent biocompatibility. At intermediate pH behave as Zwitterionic. Eg: Lecithin, N- dodycylalanine

Factors affecting the Formulation of Nanoemulsion[27]:

The formation of stable transparent nanoemulsions poses two challenges: the ability to initially create an emulsion where the entire droplet size distribution is below 80 nm, and the subsequent stabilization of this emulsion against Ostwald ripening. Appropriate composition is required to avoid Oswald ripening. The dispersed phase should be highly insoluble in the dispersed medium.

I. The surfactant is an essential part of the nanoemulsion. They should not form lyotropic liquid

crystalline “microemulsion” phases.

II. The presence of excess surfactants enables new surface area of nanoscale to be rapidly coated

during emulsification there by inhibiting induced coalescence.

III. Extreme share must be applied to rupture microscale droplets to nanoscale by providing the stress

level to reach above the Laplace pressure of the droplets with a pressure of 10- 100 atm. Out of various methods ultrasonication is widely used in laboratory.

Preparation Methods Of Nanoemulsions:[28]:

For the preparation of nanoemulsion drug is dissolved in lipophilic part (oil). Aqueous phase (water) can be mixed with surfactant and cosurfactant is then added at slow rate with gradual stirring until the system is transparent. The amount of surfactant and cosurfactant to be added and the percent of oil phase that can be incorporated shall be determined with the help of pseudo-ternary phase diagram. Ultrasonicator can finally be used so to achieve the desired size range for dispersed globules. It is then being allowed to equilibrate.

Factors required for nanoemulsion preparation[29]:

Three important conditions:

i. Surfactants must be critically evaluated so that an ultra-low interfacial tension (< 10-3 mN/m) can be attained at the oil / water interface which is a prime requirement to produce nanoemulsions. ii. Surfactant concentration must be high enough to provide the number of surfactant molecules needed to stabilize the microdroplets to be produced by an ultra-low interfacial tension. iii. The interface must be flexible or fluid enough to promote the formation of nanoemulsions.


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

Construction of Phase Diagram:

Pseudo-ternary phase diagrams of oil, water, and cosurfactant/surfactants mixtures are constructed at fixed cosurfactant/surfactant weight ratios. Phase diagrams are obtained by mixing of the ingredients, which shall be pre-weighed into glass vials and titrated with water and stirred well at room temperature[30]. Formation of monophasic/biphasic system is confirmed by visual inspection. In case turbidity appears followed by a phase separation, the samples shall be considered as biphasic. In case monophasic, clear and transparent mixtures are visualized after stirring; the samples shall be marked as points in the phase diagram. The area covered by these points is considered as the nanoemulsion region of existence[31]Several methods have been suggested for the preparation of nanoemulsion. Here some methods are discussed which are freely used for the nanoemulsion preparation.

which are freely used for the nanoemulsion preparation. Fig. 2: Ternary phase diagram Phase Inversion Method:

Fig. 2: Ternary phase diagram

Phase Inversion Method:

In this method, fine dispersion is obtained by chemical energy resulting of phase transitions occur through emulsification method. The adequate phase transitions are produced by changing the composition at constant temperature or by changing the temperature at constant composition. Phase inversion temperature (PIT) method was introduced by Shinoda et al. based on principle of the changes of solubility of polyoxyethylene-type surfactant with temperature. This surfactant becomes lipophilic as increase in temperature because of dehydration of polymer chain. At low temperature, the surfactant monolayer has a great positive spontaneous curvature forming oil swollen micellar solution phase[32].

Sonication Method:

Sonication method is best way to prepare nanoemulsions. In sonication method the droplet size of conventional emulsion or microemulsions are reduced with the help of sonication mechanism. This method is not applicable for large batches, but only small batches of nanoemulsions can be prepared by this method.

Ultrasonic System[33]:

In ultrasonic emulsification, the energy input is provided through so called sonotrodes (sonicator probe) containing piezoelectric quartz crystals that can be expand and contract in response to alternating electrical voltage. As the tip of sonicator probe contacts the liquid, it generates mechanical vibration and therefore cavitations occurs, which is the main phenomenon responsible for ultrasonically induced effects. Cavitation is the formation and collapse of vapour cavities in a flowing liquid. Such a vapour cavity forms when the local pressure is reduced to that of at the temperature of the flowing liquid because of local velocity changes. The collapse of these cavities causes powerful shock waves to radiate throughout the solution in proximity to the radiating face of the tip, thereby breaking the dispersed droplets. Within the ultrasound range, the power available varies inversely with the frequency and only powerful ultrasound (0-200kHz) is able to produce physical and chemical changes such as emulsification. Ultrasound can be used directly to produce emulsion, but since breaking an interface requires a large amount of energy, it is better to prepare coarse emulsion before applying acoustic power. Due to small product throughput the ultrasound emulsification process mainly applied in laboratories where emulsion droplet size as low as 0.2 micrometer can be obtained.


It is possible to produce emulsion at much higher pressures up to approximately 700 Mpa, in the nozzle of microfludizer that is the heart of this device (the interaction chamber) two jets of crude emulsion from two opposite channels collide with one another. The process stream is delivered by a pneumatically powered pump that is capable of pressurizing the in-house compressed air (150-650 Mpa) up to about 150Mpa. Forcing the flow stream by high pressure through microchannels toward an impingement area creates a tremendous shearing action, which can provide an exceptionally fine emulsion[34]


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

Jet Disperser:

Forcing the flow stream by high pressure through microchannels towards an impregnated area creates a tremendous shearing action, which can provide an exceptionally fine emulsion. In general, initial forces in turbulent flow along with cavitations are predominantly responsible for droplet disruption in microfludizer. Disruption in laminar elongation flow is also possible, especially when emulsion has high viscosity. In the jet disperser two or more jets of crude emulsion each from opposing bores collide with one another but at a different design than microfludizer, the diameter of the bores in jet dispersers are typically 0.3-0.5mm. Finally an “orifice plate” is the simplest construction form for a homogenizing nozzle. The diameter of orifice bore is of same order of magnitude as the jet dispersers and inlet head diameter of orifice plate is typically 10- 60nm, in jet dispersers & orifice plates, droplets are disrupted predominantly due to laminar elongation flow ahead of the bores. Unlike radial diffusers, the nozzle is microfludizer; jet dispersers and orifice plate contain no moving parts, so they can be used at high pressures up to 300-400 Mpa [35].

Physicochemical Characterization Of Nanoemulsions[36-42]:

Table 5: Physicochemical Characterization of Nanoemulsions

S. No





Dye Solubilization


water soluble dye is solubilized within the aqueous phase of the w/o globule but is

dispersible in the o/w globule. An oil soluble dye is solubilized within the oil phase of the o/w globule but is dispersible in the w/o globule.




o/w nanoemulsions are dilutable with water whereas w/o are not and undergo phase inversion into o/w nanoemulsion.




Many oils exhibit fluorescence when exposed to UVlight. When a w/o nanoemulsion is exposed to a fluorescence light under a microscope, the entire field fluoresces. If the fluorescence is spotty, the nanoemulsion will be o/w type.


Filter paper


This test is based on the fact that an o/w nanoemulsion willspread out rapidly when dropped onto filter paper. Incontrast, a w/o nanoemulsion will migrate only slowly.This method should not be used for highly viscous creams




o/w nanoemulsion where the external phase is water are highly conducting whereas w/o are not, since water is the internal or dispersal phase.




determine the temperature of the continuous phase and to detect phase inversion phenomena, the

electrical conductivity measurements are highly useful.



sharp increase in conductivity in certain w/o nanoemulsion systems was observed at low

volume fractions and such behaviour was interpreted as an indication of a ‘percolativebehaviour’ or exchange of ions between droplets before the formation of

bicontinuous structures. Dielectric measurements are a powerful means of probing both structural and dynamic features of Nanoemulsion systems.




The DLS measurements are taken at 90° in a dynamic light scattering spectrophotometer which uses a neon laser of wavelength 632 nm. The data processing is done in the built-in computer with the instrument.




Drug content


Preweighednanoemulsion is extracted by dissolving in asuitable solvent, extract is analyzed by spectrophotometeror HPLC against standard solution of drug




The average diameters and Polydispersity index of samples were measured by Photon Correlation Spectroscopy. The measurements were performed at 25°C using a He-Ne laser.


Phase analysis



is used to determine the type of nanoemulsion (o/w or w/o) by measuring the electrical


conductivity using aconductometer.



Particle size analysis


Photon Correlation Spectrometer is used to monitor the particle size of nanoemulsions. Light

scattering are monitor at 90° angle and 25°C of temperature.





Rheological measurements are performed at 25±0.1°C using a Bohlin rheometer equipped with a cone/plate apparatus 40 mm per 4°. For each sample, continuous variation of shear rate γ is applied and the resulting shear stress σ is measured. Viscosity of dispersions with Newtonian flow properties is calculated according to the relation: η=σ/γ.



Refractive Index

Refractive index is determined at 25 ° C using refractometer.



Surface Tension












thermostatically controlled

processor tensiometer K100.







of the formulation ismeasured at 25°C using digital pH meter and the osmotic pressure



measured using micro osmometer.






observe the morphology of the oil droplets in the nanoemulsion, each batch also characterized by


TEM using a negative staining technique.







The viscosity of the formulations is determined as such without dilution using a Brookfield DV III ultra V6.0 RV cone and plate rheometer at 25 0 C ± 0.3.





Electrical conductivity of the samples ismeasured using a conductivity meter having acell constant of 0.11 cm-1 at the frequency of 94Hz. The measurements were performed intriplicate at 25 ± 1 ºC.






Percentage transmittance of the prepared nanoemulsion formulation is determined spectrophotometrically. The formulation has the highest percentage transmittance or close to 100% indicated that formulation is clear and transparent. One ml of the formulation is diluted 100 times using solvent and analyzed at λmax against solvent as blank.




Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

19 Thermodynamic


Heating cooling cycle:Six cycles between refrigerator temperature 4°C and 45°C with storage at each temperature of not less than 48 h is studied. Those formulation which are stable at these temperature, is subjected tocentrifugation test. Centrifugation:Passed formulation is centrifuged at 3500 rpm for 30 min. Those formulations that do not show any phase separation are taken for freeze thaw stress test. Freeze thaw cycle:Three freeze thaw cycle between -21°C & 25°C with storage at each temperature for not less than 48 h is done for the formulation. Those formulation which passed thermodynamic stress test, are further taken for dispersibility test forassessing the efficiency of emulsification

stability studies

20 drug



Dissolution studies or skin permeation studies is performed on the basis of delivery system.








21 Pharmacokinetic


Performed animal studies on basis of delivery system by using specific animal models.




Applications Of Nanoemulsion:

Nanoemulsion show great promise for the future of cosmetics, diagnostics, drug therapies and biotechnologies. Nanoemulsions containing pharmaceutically active agents can be utilized for the production of pharmaceutical preparations[43].

Ocular Delivery:

Oil in water emulsions are being explored for improved topical lipophilic drug delivery to the eye. Lipophilic drug loaded o/w ocular emulsions provide equivocally a better balance between ocular bioavailability improvement and patient comfort following topical instillation into the eye e.g. Piroxicam, pilocarpine, indomethacin, cyclosporine A. For the treatment of eye diseases, drugs are essentially delivered topically. O/Wnanoemulsions have been investigated for ocular administration, to dissolve poorly soluble drugs, to increase absorption and to attain prolong release profile. The nanoemulsions containing pilocarpine were formulated using lecithin, propylene glycol and PEG 200 as co- surfactant and IPM as the oil phase.[44].

Percutaneous Route:

Many drugs exhibit low skin penetration, which results in poor efficacy. As opposed to common chemical skin penetration enhancers, organic solvents are generally associated with some degree of skin irritation, toxicity and sensitization. A solvent free topical vehicle based on drug entrapment in the o/w emulsion with droplets of submicron size is more efficacious in terms of percutaneous absorption along with possibly devoid of adverse effects. In addition, the uniqueness of the large internal hydrophobic core of o/w submicronized emulsion droplets allows high solubilization capacity for water insoluble topically active medicaments.It also aids in carrying water, an excellent softener, to the skin e.g. NSAIDs, diazepam, α-tocopherol, antifungal drugs (econazole or miconazole nitrate) [45], EMLA (Eutectic mixtures of local anaesthetic) has proven to be a useful medication for children. It is an emulsion containing a mixture of lidocaine and prilocaine [46].

Nasal Route:

The nasal route has received great attention due to number of advantages over parenteral and oral administration especially by-passing the liver. Nanoemulsions increase absorption by solubilizing the drug in the inner phase of an emulsion and prolonging contact time between emulsion droplets and nasal mucosa e.g. a lipid soluble rennin-inhibitor was incorporated into an o/w emulsion. Enhanced and prolonged in vivo nasal absorption was observed in emulsion compared to aqueous suspension. Other drugs which have been formulated for nasal delivery are insulin and testosterone[47].

Pulmonary Delivery:

A novel pressurized aerosol system has been devised for the pulmonary delivery of salbutamol using lecithin stabilized microemulsions formulated in trichlorotrifluoroethane[48].

In Biotechnology:

Many enzymes including lipases, esterases, hydrogenases, and oxidases often function in cells in microenvironments that are hydrophobic in nature. In biological systems many enzymes operate at interface between hydrophobic and hydrophilic domains and these usually interfaces are stabilize by polar lipids and other natural ampiphiles. Enzymatic catalysis in nanoemulsions has been used for a variety of reactions, such as synthesis of esters, peptides and sugar acetals trans-esterification, various hydrolysis reactions and steroid transformation. The most widely used class of enzymes in microemulsion based reactions is of lipases.


Sarfaraz Ahmad et al, 2016

Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

Prophylactic in Bio-Terrorism Attack:

Nanoemulsions are used as a prophylactic medication and are used against bio-attack pathogens such as anthrax and ebola.

Nanoemulsion as Mucosal Vaccines:

Nanoemulsionscan be used forneedle free immunization bydelivering recombinant protein and inactivatedorganism to a mucosal surface as nanoemulsioncause the protein surface to be adjuvanted andthus facilitates uptake by antigen-presenting cells.

Nanoemulsion formulation of cyclosporine:

A nanoemulsion formulation of cyclosporine has been introduced to replace Sandimmune®, a crude oil-in- water emulsion of cyclosporine formulation. Neoral® is formulated with a finer dispersion, giving it a more rapid and predictable absorption and less inter and intra patient variability.

Nanoemulsion in Cell Culture Technology:

Nanoemulsions are used in cell culture technologybecause they increase uptake of oil solublecomponent in cell culture and improve growth ofculture cell.

Oral Drug Delivery System:

Formulations were developed to enhance oral bioavailability of hydrophobic drugs like paclitaxel, ramipril, celecoxib and ubiquinone. It can be used to improve oral bioavailability of poorlyto soluble drug because it has a very small particle size[49].

Transdermal Drug Delivery System (TDDS):

Nanoemulsion canbe used for transdermal drug delivery due to increased permeation through the skin. Indomethacin a potent NSAID, the anti-inflammatory effects of true optimized nanoemulsion formulation were compared with marketed gel in carragenan induced paw edema in rats. The % inhibition value was significant for developed Nanoemulsion,so great potential for transdermal application of indomethacin [50].Transdermal route by means of nanoemulsion technique has been considered to eliminate oral GI adverse effects, maintains the plasma drug level for longer period of time, improve patient compliance and suitable for long treatment of arthritis.


Nanoemulsions have been widely increasing as potential vehicles for the controlled delivery of cosmetics and for the optimized dispersion of active ingredients in particular skin layers. It is increasingly used in the cosmetic because the active constituents are easily absorbed to give effective action due to small size of droplets and reduce the water loss from the skin.This may reduce the trans-epidermal water loss (TEWL), indicating that the barrier function of the skin is enhanced[51].Due to their lipohilic inner property, nanoemulsions are more suitable for the transport of lipophilic compounds than liposomes. Similar to liposomes, they 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 active to the skin. Furthermore, nanoemulsions gain increasing interest due to their own bioactive effects. Nanoemulsions are suitable in cosmetics because there is no inherent creaming, sedimentation, flocculation or coalescence


Antimicrobial Nanoemulsions:

Antimicrobialnanoemulsions areo/w droplet which has a broad-spectrum activity against bacteria (e.g., E. coli, Salmonella, S.aureus), enveloped viruses (e.g., HIV, Herpes simplex), fungi (e.g., Candida, Dermatophytes), and spores (e.g., Anthrax) [53].Nanoemulsions are droplets attached with lipid containing organisms and release part of the energy trapped within the emulsion. Pathogenlipid membrane is destabilized by active ingredient andthe energy released by the emulsion, leading to microbial cell lysis[54].

Nanoemulsions in Cancer Therapy:

Nanoemulsions are used as vehicle in cancer chemotherapy for extendingthe rate of drug release after intramuscular andintratumoral injection (w/o systems). It also improves the transport of anti-cancer drugs via lymphatic system [55, 56, 57].


Overall we can conclude nanoemulsion formulation may be considered as effective, safe and patient compliance drug delivery of pharmaceutical products. One of the distinctive characteristics of the


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Advances in Environmental Biology, 10(10) October 2016, Pages: 120-130

nanoemulsion technology is the relatively high percentage of total particle volume occupied by the internal hydrophobic oil core of the droplets. In future further research work and development will be carried out for clinical application of nanoemulsion formulation.


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