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Development of Nanoemulsion by emulsification

evaporation technique
1) Ashwanth Subramanian1
Rashtreeya Vidyalaya College of Engineering, Bangalore India
ashwanth1809@yahoo.in

Abstract- This is a report on the development of nanoemulsion by the emulsification evaporation

technique. Researches in the nanoemulsion field have increased over the years due to their
attractive properties, their advantageous over the conventional materials and the new possibilities
in various areas which eliminates the difficulties of the conventional methods. This is a report on
the emulsion synthesis by the emulsification evaporation technique followed by application of
nanoemulsions in biochemical engineering, mass transfer, chemical equipment design drawing
and nanotechnology.

I.

INTRODUCTION

Nanoemulsions are submicron sized emulsion that is under extensive investigation as drug carriers
for improving the delivery of therapeutic agents. These are by far the most advanced nanoparticle
systems for the systemic delivery of active pharmaceutical for controlled drug delivery and targeting.
These are the thermodynamically stable isotropic system in which two immiscible liquid (water and
oil) are mixed to form a single phase by means of an appropriate surfactants or it mixes with a
droplet diameter approximately in the range of 0.5-100 m. Nanoemulsion droplet size falls typically
in the range of 20-200 nm and shows a narrow size distribution. Nanoemulsion show great promise
for the future of cosmetics, diagnostics, drug therapies and biotechnologies. Thus the aim of this
review is focused on nanoemulsion advantage and disadvantage, various methods of preparation,
characterization techniques and the various applications of sub-micron size emulsion in different
areas such as various route of administration, in chemotherapy, in cosmetic, etc.
Nanoemulsions can be defined as oil-in-water (o/w) emulsions with mean droplet diameters ranging
from 50 to 1000 nm. Usually, the average droplet size is between 100 and 500 nm, terms sub-micron
emulsion (SME) and mini-emulsion are used as synonyms. Since, the preparation of the first
nanoemulsion in 1940s, it can be of three types such as oil-in-water (o/w), water- in-oil (w/o), and bicontinuous. The transformation between these three types can be achieved by varying the
components of the emulsions. Each type of the nanoemulsions serves as a template for preparing
polymer latex particles, nonporous polymeric solids etc. Apart from this, the nanoemulsions with
pharmaceutically accepted ingredients are utilized in the development of drug formulations for oral
drug delivery. The nanoemulsions are also referred as miniemulsions, ultrafine emulsions and
submicron emulsions. Phase behaviour studies have shown that the size of the droplets is governed
by the surfactant phase structure (bicontinuous microemulsion or lamellar) at the inversion point
induced by either temperature or composition. Studies on Nanoemulsion formation by the phase
inversion temperature method have shown a relationship between minimum droplet size and
complete solubilization of the oil in a microemulsion bicontinuous phase independently of whether
the initial phase equilibrium is single or multiphase. Due to their small droplet size, nanoemulsions
possess stability against sedimentation or creaming with Ostwald ripening forming the main

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mechanism of nanoemulsion breakdown. The main application of nanoemulsions is the preparation

of nanoparticles using a polymerizable monomer as the disperse phase (the so-called miniemulsion
polymerization method) where nanoemulsion droplets act as nanoreactors. Another interesting
application which is experiencing an active development is the use of Nanoemulsions as
formulations, namely, for controlled drug delivery and targeting. The main application of
nanoemulsions is the preparation of nanoparticles using a polymerizable monomer as the disperse
phase where nanoemulsion droplets act as nanoreactors.
Advantages of Nanoemulsion :

The nano-sized droplets leading to enormous interfacial areas associated with nanoemulsions
would influence the transport properties of the drug, an important factor in sustained and
targeted drug delivery.
Nanoemulsions have been reported to make the plasma concentration profiles and
bioavailability of drugs more reproducible.
Fine oil droplets empty rapidly from the stomach and promote wide distribution of the drug
throughout the intestinal tract and thereby minimizing irritation frequently encountered with
extended contact of the drug and gut wall.
Higher solubilization capacity than simple micellar solutions and their thermodynamic
stability offers advantages over unstable dispersions such as emulsions and suspensions
because they can be manufactured with little energy input (heat or mixing) and have a long
shelf life.
They also provide ultra-low interfacial tension and large o/w interfacial areas.
They also offer an advantage over existing self-emulsifying system in terms of rapid onset of
action (no extra time for dispersion) and reduced intersubjective variability in terms of GIT
fluid volume. They possess high kinetic stability and optical transparency resembling to
microemulsions.
The structures in the nanoemulsions are much smaller than the visible wavelength, so most
nanoemulsions appear optically transparent, even at large loading.
They have potential to deliver peptides that are prone to enzymatic hydrolysis in GIT.
Nanoemulsions have higher surface area and higher free energy than macro emulsions that
make them an effective transport system.
Problems of inherent creaming, flocculation, coalescence, and sedimentation are not seen in
nanoemulsions, which are commonly associated with macroemulsions.
Nanoemulsions can be formulated in numerous dosage foam such as creams, liquids, sprays
and foams.
It is non-toxic and non-irritant so can be easily applied to skin and mucous membranes.
Nanoemulsions is formulated with surfactants, which are approved for human consumption
(GRAS) so they can be taken by enteric route.
It is do not damage healthy human and animal cells, so nanoemulsions are suitable for human
and veterinary therapeutic purposes.

II.

BIOCHEMICAL ---APPLICATION OF NANOEMULSION

The specific capture and detection of nucleic acid molecules (DNA or RNA) in biomedical
diagnostic have attracted special interest in the last 20 years. In order to enhance the specificity and
the sensitivity of molecular diagnostic, special attention has been paid to the possible automation of
samples preparation, specific or generic extraction of DNA molecules, and specific target detection

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in new biotechnological devices. To answer the variability of conditions encountered by the different
types of nucleic acids, various supports have been used and widely explored. Several devices were
used as solid supports for biomolecules immobilization. .In this direction, the chemical grafting of
single stranded DNA (ss DNA) fragments (capture probes) on selected solid support) has been
applied to the capture of nucleic acid molecules. The specificity of this capture is controlled by the
hydrogen binding between complementary bases.
The detection is hereafter performed by coupling a complementary ss DNA bearing enzyme
sequence to a given part of the target. Then, the addition of a chemical specie that is transformed by
the enzyme results in a colouring of the system. A colorimetric titration leads directly to the target
captured amount. As a general tendency, the specific capture efficiency is related to
(i)
The accessibility and the reactivity of the capture probes,
(ii)
The surface properties of the solid support,
(iii)
The affinity between the solid support surface and the target probes, and
(iv)
The amount of target in the biological sample.
Using magnetic colloids, various problems have been solved or at less circumvented as evidenced by
the numerous reported works. Such colloids have been used in various levels of bionanotechnologies. Apart from their large specific area, their main advantage is their ability to move
under the application of a single magnetic field, which allows for their separation from the
surrounding medium. Magnetic particles have been widely used in various biomedical applications,
such as immunoassays, bacteria isolation, cell sorting, virus extraction, and finally generic nucleic
acids. In this direction, magnetic emulsions were used as seed in emulsion polymerization processes.
The advantages of magnetic emulsions are their narrow size distribution, high iron oxide content, and
their ability to be turned into magnetic latex particles as an appropriate polymerization process
occurs.
In the last decade, it was shown that the repulsive forces between magnetic emulsion droplets could
be measured and used to determine the presence of charges or adsorbed macromolecules at the
particles surface. More precisely, it was demonstrated that even the conformation and density
number of adsorbed macromolecules could be determined using such measurements.
Streptavidin-Magnetic Droplets Conjugates Preparation:
The oligonucleotides or ss DNA molecules bearing biotin at the 50 position are immobilized onto the
streptavidin containing oil in water magnetic ferro-fluid nanodroplets. The streptavidin is chemically
grafted on to activated carboxylic groups of the nanodroplets surface. After chemical grafting, the
emulsion droplets bearing ss DNA capture probe are washed via magnetic separation-redispersing
cycles using a TE buffer solution (10m MTris; 1M NaCl,10m MEDTA, 0.05wt%TritonX-405).In
order to avoid the adsorption of the capture and detection probes on the nanodroplets, well
appropriate amount of salmon DNA (low molecular weight) is introduced in streptavidin containing
magnetic nanodroplets dispersion as a coating agent
The capture probe (ssDNA grafted consists in 32 nucleotides complementary to HIV nucleic acid
sequence used as a target model. The obtained mixtures are then incubated at 37C for 30min before
the washing step.
Specic Capture and Detection of the Nucleic Acid Target (ELOSA):

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Enzyme Linked Oligo Sorbent Assay (ELOSA) is used in biomedical diagnostic for specified
detection of nucleic acid target via specific hydrogen binding as shown. The capture probe-magnetic
particle conjugates are mixed with ss DNA solution composed of HIV sequence containing 72
nucleotides as a model of target nucleic acid materials. The detection process of the captured HIV
target is performed by adding a second ssDNA (named detection probe) of 29 nucleotides bearing
HRP enzyme (Horse Radish Peroxydase) at its extremity The added substrate is oxidized by HRP
leading to colored medium, which quantified by UV spectrophotometer. The intensity of the
coloration is quantified using a UV spectrometer at 492nm wavelength.
This study is necessary in order to evaluate the specificity and the accessibility of the capture probes.
This ELOSA method clearly reveals the presence of detection ssDNA at the surface of the magnetic
particles. In addition, the amount of ssDNA (capture probe) at the magnetic particles surface
increases as a function of streptavidin immobilized amount on the particles before reaching the
surface saturation. It is interesting to notice that ELOSA technique is not quantitative and can be
used for the qualitative and comparative aspects only.

Figure 1: Schematic presentation of the system after each different step of the coupling and capture
procedure
Antibacterial Nanoemulsion :
Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing
presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial
therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and
water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria,
enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion
preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation
for further evaluation.
Over the past 15 years, Acinetobacter baumannii (an aerobic, Gram-negative coccobacillus) has
become an emerging problematic pathogen with a wide array of antibiotic resistance, representing a
serious threat not only to civilian hospital patients but also to military service members wounded in
Iraq and Afghanistan. Despite many approaches to find available treatment options, A. baumanniis

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low permeability of the outer membrane, its ability to acquire genetic elements efficiently, and its
ability to establish biofilms have made treatment options limited.
Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (particle size, 100
to 800 nm) which have been shown to have broad antimicrobial activity against bacteria, enveloped
viruses, and fungi at concentrations that are nontoxic in animals. When nanoemulsions function by
fusing with lipid bilayers of cell membranes, the energy stored in the oil-and-detergent emulsion is
released and destabilizes the lipid membrane of the bacteria; hence their antimicrobial activity . The
antimicrobial activity of nanoemulsions is nonspecific, unlike that of antibiotics, thus allowing
broad-spectrum activity while limiting the capacity for the generation of resistance. These features
make nanoemulsion a suitable candidate for both wound treatment and surface decontamination.
Cetylpyridinium chloride (CPC) is a quaternary ammonium salt which has been utilized as an
antimicrobial and disinfectant in many commercially available mouthwashes, toothpastes, lozenges,
throat sprays, breath sprays, and nasal sprays. Quaternary ammonium compounds are active against
bacteria through multiple mechanisms, with activity being maintained when the compound is
incorporated into nanoemulsion formulations.
Cetylpyridinium chloride (CPC) is a quaternary ammonium salt which has been utilized as an
antimicrobial and disinfectant in many commercially available mouthwashes, toothpastes, lozenges,
throat sprays, breath sprays, and nasal sprays. Quaternary ammonium compounds are active against
bacteria through multiple mechanisms, with activity being maintained when the compound is
incorporated into nanoemulsion formulations.

Figure 2: Antibacterial Nanoemulsion

The active ingredient and the high energy are essential for the antimicrobial mechanism of action.
Additional reduction of size is achieved by a high-pressure microfluidizer. This additional reduction
of size results in more energy units per volume. Additional ingredients are added to enhance the
nanoemulsion spectrum of activity or to improve its stability. The concentrated (neat) emulsions are

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diluted 10- to 100-fold in water, resulting in a stable final product. The dilute emulsions are milky in
consistency and appearance; additional thickeners could be added to increase its viscosity and
prevent running in specific applications.
The nanoemulsion 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). See our section on nanoemuslion as a decontamination agent. The
nanoemulsion particles are thermodynamically driven to fuse with lipid-containing organisms. This
fusion is enhanced by the electrostatic attraction between the cationic charge of the emulsion and the
anionic charge on the pathogen. When enough nanoparticles fuse with the pathogens, they release
part of the energy trapped within the emulsion. Both the active ingredient and the energy released
destabilize the pathogen lipid membrane, resulting in cell lysis and death.

Figure 3: Attack of nanoemulsion on microorganism

A unique aspect of the nanoemulsions is their selective toxicity to microbes at concentrations that are
non-irritating to skin or mucous membrane. This safety has been tested in several animal species and
verified during human clinical trials. The safety margin of the nanoemulsion is due to the low level
of detergent in each droplet, yet when acting in concert, these droplets have sufficient energy and
surfactant 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. Nanoemulsion cannot, however, be injected into the bloodstream
because they will lyse red cells.
Other Applications of Nanoemulsion:
1. Use of nanoemulsions in cosmetics:
Nanoemulsions have recently become increasingly important as potential vehicles for the controlled
delivery of cosmetics and for the optimized dispersion of active ingredients in particular skin layers.
Due to their lipophilic interior, nanoemulsions are more suitable for the transport of lipophilic
compounds than liposomes. Similar to liposomes, they support the skin penetration of active

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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. This may reduce the transepidermal water loss (TEWL), indicating that the barrier function of the skin is strengthened.
Nanoemulsions are acceptable in cosmetics because there is no inherent creaming, sedimentation,
flocculation or coalescence observed within macroemulsions. The incorporation of potentially
irritating surfactants can often be avoided by using high-energy equipment during manufacturing.
2. Prophylactic in Bio-Terrorism Attack. :
Based on their antimicrobial activity, research has begun on use of nanoemulsions as a prophylactic
medication, a human protective treatment, to protect people exposed to bio-attack pathogens such as
Anthrax and Ebola. A broad-spectrum nanoemulsion was tested on surfaces by the US Army
(RestOps) in Dec 1999 for decontamination of Anthrax spore surrogates. It was tested again by
RestOps in March 2001 as a chemical decontamination agent. All tests were successful. The
technology has been tested on gangrene and clostridium botulism spores and can even be used on
contaminated wounds to salvage limbs. The nanoemulsion technology can be formulated into a
cream, foam, liquid or spray to decontaminate a variety of materials.
3. Nanoemulsions as Mucosal Vaccines:
Nanoemulsions are being used to deliver either recombinant proteins or inactivated organisms to a
mucosal surface to produce an immune response. The first applications, an influenza vaccine and an
HIV vaccine, can proceed to clinical trials.
The nanoemulsion causes proteins applied to the mucosal surface to be adjuvanted, 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.
Initial work in influenza has demonstrated that animals can be protected against influenza after just a
single mucosal exposure to the virus mixed with the emulsion. Research has also demonstrated that
animals exposed to recombinant gp120 in nanoemulsion on their nasal mucosa develop significant
responses to HIV, thus providing a basis to examine the use of this material as an HIV vaccine.
Additional research is ongoing t complete the proof of concept in animal trials for other vaccines
including Hepatitis B and Anthrax.
4. Nanoemulsion as Non-Toxic Disinfectant Cleaner:
A breakthrough nontoxic disinfectant cleaner for use in commercial markets that include healthcare,
hospitality, travel, food processing and military applications has been developed by EnviroSystems,
Inc. kills tuberculosis and a wide spectrum of viruses, bacteria and fungi in five to 10 minutes
without any of the hazards posed by other categories of disinfectants. The product needs no warning
labels. It does not irritate eyes and can be absorbed through the skin, inhaled or swallowed without
harmful effects. The disinfectant formulation is made up of Nanospheres of oil droplets
<=106mwhich are suspended in water to create a nanoemulsion 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 one-to-two orders of magnitude lower than those of
other disinfectants, hence there are no toxic effects on people, animals or the environment. Other

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microbial disinfectants require large doses of their respective active ingredients to surround pathogen
cell walls, which causes them to disintegrate, fundamentally 'drowning' them in the disinfectant
solution.
The disinfectant is nonflammable and therefore safe to store most anywhere and also to use in
unstable conditions. It is nonoxidizing, nonacidic and non-ionic. It won't corrode plastic, metals or
acrylic, making the product ideal for use on equipment and instruments. It is environmentally safe
hence the costs and health risks associated with hazardous chemical disposal are eliminated.
The formulation is a broad-spectrum disinfectant cleaner that can be applied to any hard surface,
including equipment, counters, walls, fixtures and floors. One product can now take the place of
many, reducing product inventories and saving valuable storage space. Chemical disposal costs can
be eliminated, and disinfection and cleaning costs can be reduced.
5. Nanoemulsions in Cell Culture Technology:
Cell cultures are used for in vitro assays or to produce biological compounds, such as antibodies or
recombinant proteins. To optimize cell growth, the culture medium can be supplemented with a
number of defined molecules or with blood serum. Up to now, it has been very difficult to
supplement the media with oil-soluble substances that are available to the cells, and only small
amounts of these lipophilic compounds could be absorbed by the cells.
Nanoemulsions are a new method for the delivery of oil-soluble substances to mammalian cell
cultures. The delivery system is based on a nanoemulsion, which is stabilized by phospholipids.
These nanoemulsions are transparent and can be passed through 0.1-m filters for sterilization.
Nanoemulsion droplets are easily taken up by the cells. The encapsulated oil-soluble substances
therefore have a high bioavailability to cells in culture. 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.
6.
7.
8.
9.

Nanoemulsion formulations for improved oral delivery of poorly soluble drug.

Self-nanoemulsifying drug delivery systems.
Nanoemulsions as a vehicle for transdermal delivery.
Nanoemulsion in the treatment of various other disease conditions like diclofenac cream, a
potential treatment for osteoarthritis.
10. Solid self-nanoemulsifying delivery systems as a platform technology for formulation of
poorly soluble drugs.
11. Nanoemulsion in cancer therapy and in targeted drug delivery.

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III.

NANOTECHNOLOGYPREPARATION AND CHARACTERIZATION TECHNIQUES

Factors to be considered during preparation of nanoemulsion:

Three important conditions:
* Surfactants must be carefully chosen 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.
* Concentration of surfactant must be high enough to provide the number of surfactant molecules
needed to stabilize the nano droplets to be produced by an ultra-low interfacial tension.
* The interface must be flexible or fluid enough to promote the formation of nanoemulsions.
Nanoemulsion, being non-equilibrium systems cannot be formed spontaneously. Consequently,
energy input generally from mechanical devices or from the chemical potential of the components is
required, Nanoemulsion formation by the so called dispersion or high energy emulsification method
is generally achieved using high shear stirring, high pressure homogenizers and ultrasound
generators. It has been shown that the apparatus supplying the available energy in the shortest time
and having the most homogeneous flow produces the smaller sizes. High pressure homogenizers
meet these requirements; therefore, they are the most widely used emulsifying machines to prepare
nanoemulsion. Generally, the conventional high pressure homogenizers work in a range of pressures
between 50 and 100 Mpa. Pressure as high as 350Mpa have been achieved in a recently developed
instrument. Ultrasonication emulsification is also very efficient in reducing droplet size but it is
appropriate for small batches. On the preparation of polymerizable nanoemulsion has shown that the
efficiency of dispersion process is strongly dependent on ultrasonication time at different amplitudes
and that the more hydrophobic the monomer is the longer the sonication time required.
Techniques of preparation of nanoemulsion:
1. High-Pressure Homogenisation:
The preparation of nanoemulsions requires high- pressure homogenization. This technique makes
use of high- pressure homogenizer/piston homogenizer to produce nanoemulsions of extremely low
particle size (up to 1nm). 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. The particles which are formed exhibit a liquid,
lipophilic core separated from the surrounding aqueous phase by a monomolecular layer of
phospholipids. This technique has great efficiency, the only disadvantage being high energy
consumption and increase in temperature of emulsion during processing.
2. Microfluidization:
Microfluidization is a mixing technique, which makes 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

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of sub- micron range. The two solutions (aqueous phase and oily phase) are combined together and
processed in an inline homogenizer to yield a coarse emulsion. The coarse emulsion is into a
microfluidizer where it is further processed to obtain a stable nanoemulsion. The coarse emulsion is
passed through the interaction chamber microfluidizer repeatedly until desired particle size is
obtained. The bulk emulsion is then filtered through a filter under nitrogen to remove large droplets
resulting in a uniform nanoemulsion.
3. Spontaneous Emulsification:
It involves three main steps:
* Preparation of homogeneous organic solution composed of oil and lipophilic surfactant in water
miscible solvent and hydrophilic surfactant.
* The organic phase was injected in the aqueous phase under magnetic stirring the o/w emulsion was
formed.
* The water-miscible solvent was removed by evaporation under reduced pressure.
4. Low Energy Emulsification:
This Technique is used for the preparation of o/w nanoemulsion. Take advantage of the
physicochemical properties of these systems based on the phase transition that takes place during the
emulsification process.
5. Hydrogel Method:
It is similar to solvent evaporation technique. The only difference between the two methods is that
the drug solvent is miscible with the drug anti-solvent. Higher shear force prevent crystal growth and
Ostwald ripening. Other method used for Nanoemulsion preparation is the phase inversion
temperature technique.
6. Solvent evaporation:
Solvent Evaporation Technique: This technique involves preparing a solution followed by its
emulsification in another liquid that is non- solvent for the emulsion. Evaporation of the solvent
leads to precipitation of the drug. Crystal growth and particle aggregation can be controlled by
creating high shear forces using a high-speed stirrer.
Aqueous phase for the emulsion is prepared (Majority water).
Organic phase for the emulsion is prepared (oil + surfactant in an organic solvent).
Organic phase is added to the aqueous phase and mixed to get a homogeneous mixture.
(Emulsification takes place in this step)
The homogeneous mixture is passed through a high pressure homogenizer in which droplet
size reduction takes place.
The organic solvent is evaporated from the emulsion using suitable apparatus.
7. Ultrasonic Emulsification:
In ultrasonic emulsification, the energy input is provided through so called sonotrodes (sonicator
probe) containing piezoelectric quartz crystals that can be expand & 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

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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.
Characterization techniques:
Dynamic Light Scattering (DLS - also known as Photon Correlation Spectroscopy or Quasi-Elastic
Light Scattering) is one of the most popular light scattering techniques because it allows particle
sizing down to 1 nm diameter. Typical applications are emulsions, micelles, polymers, proteins,
nanoparticles or colloids. The basic principle is simple: The sample is illuminated by a laser beam
and the fluctuations of the scattered light are detected at a known scattering angle by a fast photon
detector.
Simple DLS instruments that measure at a fixed angle can determine the mean particle size in a
limited size range. More elaborated multi-angle instruments can determine the full particle size
distribution.

Figure 4: The Principle

From a microscopic point of view the particles scatter the light and thereby imprint information
about their motion. Analysis of the fluctuation of the scattered light thus yields information about the
particles. Experimentally one characterizes intensity fluctuations by computing the intensity
correlation function g2 (t), whose analysis provides the diffusion coefficient of the particles (also
known as diffusion constant).

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The diffusion coefficient D is then related to the radius R of the particles by means of the StokesEinstein Equation:
k *T
D
6 * * R *

Where k is the Boltzmann-Constant, T the temperature and

the viscosity.

The correlation of the intensity can be performed by electronic hardware or software analysis of the
photon statistics. Because fluctuation are typically in the range of nanoseconds to milliseonds,
electronic hardware is typically faster and more reliable at this job.
Data Analysis
Cumulant Method:
To obtain the diffusion coefficient the intensity correlation function must be analyzed. The standard
procedure for this is the application of the cumulant method. By fitting a polynomial of third degree
to the logarithm of the intensity correlation function, the decay rate is obtained (1. cumulant).
The decay rate is directly related to the diffusion coefficient D:

Where q is is the wave vector, which is dependend of the scattering angle.

Higher orders of the fitting result (2. and 3. cumulant) give the polydispersity index of the sample.
Modern dynamic light scattering instruments perform cumulant analysis automatically. The quality
of the result however depends significantly on the quality of the data and the constraint settings of
the fitting procedure. The cumulant analysis can only determine the particle size distribution of a
Gaussian distribution around on mean particle size. For more bi- or polymodal particle size
distributions more complex analysis methods such as the Contin method are required.
Quality of measurement:
The quality of a DLS measurement depends on several factors. Some obvious, such as the quality of
the component (the laser, the detector, the correlator...), other factors are not as straightforward but

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may influence the measurement significantly. Some important points to be considered are listed
below.
The scattering angle:
The decay rate depends on the wave vector and thus the scattering angle. Particles of different sizes
scatter with different intensities in dependence of the scattering angle. Thus there is an optimum
angle of detection for each particle size. A high quality analysis should always be performed at
several scattering angles (multiangle DLS). This becomes even more important in case of
polydisperse samples with unknown particle size distribution since at certain angles, the scattering
intensity of some particles will completely overwhelm the weak scattering signal of other particles,
thus making them invisible to the data analysis at this angle.
DLS instruments working exclusively at a fixed angle can only deliver good results for some
particles. Therefore, special attention should be paid while considering a precision of an advertised
DLS instrument. For these fixed angle instruments such indications are only ever true for certain
particles.

Figure 5: LS Spectrometer
Polydispersity Index:
The average diameters and polydispersity index of samples can be measured by photon correlation
spectroscopy. The measurements were performed at 25oC using a HeNe laser.
Viscosity Determination:
The viscosity of the formulations can be determined as such without dilution using a Brookfield DV
III ultra V6.0 RV cone and plate rheometer using spindle
Refractive Index:
The refractive index, n, of a medium is defined as the ration of the speed, c, of a wave such as light
or sound in a reference medium to the phase speed, vp, of the wave in the medium.
n=c/vp
Transmission Electron Microscopy (TEM):
Morphology and structure of the nanoemulsion can be studied using transmission electron
microscopy. Combination of bright field imaging at increasing magnification and of diffraction

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modes was used to reveal the form and size of nanoemulsion droplets. Observations can be
performed as, a drop of the nanoemulsion was directly deposited on the holey film grid and observed
after drying.

IV.

MASS TRANSFER--- GAS ABSORPTION

Gas absorption:
It is a mass transfer operation in which one or more gas solutes is removed by dissolution in a liquid.
The inert gas in the gas mixture is called carrier gas. In the absorption process of ammonia from
air-ammonia mixture by water, air is carrier gas, ammonia is solute and water is absorbent. An
intimate contact between solute gas and absorbent liquid is achieved in a suitable absorption
equipment, namely, tray tower, packed column, spray tower, venture scrubber, etc. Desorption or
stripping operation is the reverse of absorption. Absorption operation is of two types; physical and
chemical.

Single-Component Absorption:
Most absorption or stripping operations are carried out in counter current flow processes, in which
the gas flow is introduced in the bottom of the column and the liquid solvent is introduced in the top
of the column. The mathematical analysis for both the packed and plated columns is very similar.

Counter-current absorption process

The overall material balance for a countercurrent absorption process is
Lb + VT = Lt + Vb
----1
Where V = vapor flow rate L = liquid flow rate t, b = top and bottom of tower, respectively
The component material balance for species A is
LbxA, b + VT yA, t = LtxA, t + Vb yA, b -----2
Where yA = mole fraction of A in the vapor phase xA = mole fraction of A in the liquid phase

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For some problems, the use of solute-free basis can simplify the expressions. The solute-free
concentrations are defined as:

-----3a, 3b
If the carrier gas is completely insoluble in the solvent and the solvent is completely nonvolatile, the
L
carrier gas and solvent rates remain constant throughout the absorber. Using
to denote the flow
V
rate of the nonvolatile and
to denote the carrier gas flow rate, the material balance for solute A
becomes
----4
Or

----5
The material balance for solute A can be applied to any part of the column. For example, the material
balance for the top part of the column is

----6

----7
In this equation, PA is the partial pressure of species A over the solution and CA is the molar
concentration with units of mole/volume. The Henrys law constant H and m have units of
pressure/molar concentration and pressure/mole fraction, respectively. K is the equilibrium constant
or vapor-liquid equilibrium ratio.

Plate contractors:

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Plate contractors/ towers are vertical cylindrical columns in which a vertical stack of trays or plates
are installed across the column height as shown in figure. The liquid enters at the top of the column
and flows across the tray and then through a downcomer (cross-flow mode) to the next tray below.
The gas/vapor from the lower tray flows in the upward direction through the opening/holes in the
tray to form a gas-liquid dispersion. In this way, the mass transfer between the phases (gas/vaporliquid) takes place across the tray and through the column in a stage-wise manner.

Figure 6: Schematic diagram of a plate contractor

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Figure 7: Schematic of a tray operating in the froth regime

Figure 8: Typical cross-flow plate (sieve)

Plate types:
Gas and liquid flow across the tray can either be by cross-flow or counter-flow manner. The crossflow plates are most widely practiced and the three main types of cross flow plates are: bubble cap,
valve and sieve trays with downcomer.

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Figure 9: Classification of plate types based on flow mode- side view shown: (a) Cross-flow plate,
(b) Counterflow plate.
Bubble cap plates:
An enhanced gas-liquid contact can be achieved having bubble caps on the tray at very low liquid
flow rates. A bubble cap consists of a riser (also called chimney) fixed to the tray through a hole and
a cap is mounted over the riser. The gas flows up through the riser, directed downward by the cap
through the annular space between riser and cap. Finally, the gas is dispersed into the liquid. A
number of slots in the lower part of the cap help in gas bubble dispersion. Un-slotted types of cap
designs are also common in application. Bubble caps are especially suitable for higher turndown
ratio. Turndown ratio is the ratio of maximum operating vapor rate to the minimum allowable vapor
rate, below which weeping starts.

Figure 10: Bubble caps

Valve plates:
Valve trays (or floating cap plate) are the modified design of sieve trays where relatively large plate
perforations are covered by movable caps/valves .Valves cover may be round or rectangular. The
very common whole diameter is 40 mm but up to 150 mm are also used. The valve lifts up as the
vapor flow rate increases and the valve sits over the perforation at lower flow rate, thus stops the
liquid from weeping. Valve trays provide good vapor-liquid contact at low flow rates (high turndown
ratio).

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Figure 11: Valve tray

Sieve plate:
The sieve tray (also known as perforated plate) is a flat perforated metal sheet. The whole diameter
from 1.5 to 25 mm are very commonly used. The sieve tray layout is a typical square or equilateral
triangular pitch holes. The gas/vapor flows upward through the perforation and disperses into the
flowing liquid over the plate. There is no liquid seal in case of trays without downcomer and the
liquid weeps (called weeping) through the holes at low flow rates, reducing the efficiency of plate.
For this reason, sieve tray has the lowest turndown ratio. Sieve tray construction is simple and
relatively cheap.

Figure 12: Sieve tray

Selection of tray type:
The comparative performances of three common types of trays are summarized in Table The
capacity, efficiency, pressure drop and entrainment of sieve and valve trays are almost same. Bubble
cap trays have lower capacity and efficiency and but higher pressure drop and entrainment compared
to valve and sieve trays. The turndown ratio comes in the order of: bubble cap>valve>sieve.
However, valve trays have the best turndown ratio in case of refinery applications. Sieve trays are the
least expensive and suitable for almost all applications. Valve trays can be considered where higher
turndown ratio is needed. Bubble cap trays should be used at very low liquid flow rate which is not
achievable using sieve trays
Tray
type
Bubble
cap

Capacity

Efficiency

Medium
high

Medium
high

Valve

High
to High
very high

Pressure
drop
High

Entrainment

Medium
to high

Medium

~3 times
than
sieve tray

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Turndown
ratio
Excellent

4 to 10.1

Cost
100-200 %
more than
sieve
tray
20-50% more
than sieve
tray

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Sieve

High

High

Medium

Medium

2.1

Cheapest of
all types

Table 1:Comparison of three types of cross-flow trays

The centrifugal absorber:
In an attempt to obtain the benets of repeated spray formations, a centrifugal type absorber has been
developed from the ideas of Piazza for a still head. The principle of the unit is shown in figure. A set
of stationary concentric rings intermeshes with a second set of rings attached to a rotating plate.
Liquid fed to the centre of the plate is carried up the rst ring, splashes over to the bafe and falls
into the through between the rings. It then runs up the second ring and in a similar way passes from
ring to ring through the unit. The gas stream can be introduced at the top to give co-current ow, or
at the bottom if counter-current ow is desired. The depth of the ring was not very important and that
most of the transfer took place as the gas mixed with the liquid spray leaving the top of the rings.

Figure 13: Centrifugal Absorber

Spray towers:
In the spray tower, the gas enters at the bottom and the liquid is introduced through a series of sprays
at the top. The performance of these units is generally rather poor, because the droplets tend to
coalesce after they have fallen through a few metres, and the interfacial surface is thereby seriously
reduced. Although there is considerable turbulence in the gas phase, there is little circulation of the
liquid within the drops, and the resistance of the equivalent liquid lm tends to be high. Spray towers
are therefore useful only where the main resistance to mass transfer lies within the gas phase, and
have consequently been used with moderate success for the absorption of ammonia in water. They
are also used as air humidiers, in which case the whole of the resistance lies within the gas phase.

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Figure 14: Spray Tower

Centrifugal spray tower:

A spray tower in which the gas stream enters tangentially, so that the liquid drops are subjected to
centrifugal force before they are taken out of the gas stream at the top.

Figure 15: Centrifugal spray Tower

V. CEDD---PLATE COLUMN ABSORPTION TOWER DESIGN

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General Design Procedure:

1. Calculate the maximum and minimum vapour and liquid ow-rates, for the turn down ratio
required.
2. Collect, or estimate, the system physical properties.
3. Select a trial plate spacing .
4. Estimate the column diameter, based on ooding considerations .
5. Decide the liquid ow arrangement .
6. Make a trial plate layout: downcomer area, active area, whole area, whole size, weir height .
7. Check the weeping rate , if unsatisfactory return to step 6.
8. Check the plate pressure drop , if too high return to step 6.
9. Check downcomer back-up, if too high return to step 6 or 3 .
10. Decide plate layout details: calming zones, unperforated areas. Check hole pitch, if unsatisfactory
return to step 6 .
11. Recalculate the percentage ooding based on chosen column diameter.
12. Check entrainment, if too high return to step 4 .
13. Optimise design: repeat steps 3 to 12 to nd smallest diameter and plate spacing acceptable
(lowest cost).
14. Finalise design: draw up the plate specication and sketch the layout.
Effect of Vapor Flow Conditions on Tray Design:
Flooding consideration:
Excessive liquid build-up inside the column leads to column flooding condition. The nature of
flooding depends on the column operating pressure and the liquid to vapor flow ratio. It may be
downcomer backup, spray entrainment or froth entrainment type floodings. Higher tray pressure drop
due to excessive vapor flow rates holds up the liquid in the downcomer, increases the liquid level on
the plate and leads to downcomer flooding situation. The column flooding conditions sets the upper
limit of vapor velocity for steady operation.
Gas velocity through the net area at flooding condition can be estimated using fairs correlation:

----1
= vapor density, kg/m3
= liquid density, kg/m3
= liquid surface tension, mN/m (dyn/cm)
= capacity parameter (m/s) can be calculated in terms of plate spacing and flow parameter:
----2
=liquid flow rate, kg/s
=vapor flow rate, kg/s
The design gas velocities () is generally 80-85% of for non-foaming liquids and 75% or less
for foaming liquids subject to acceptable entrainment and plate pressure drop.
Sieve tray weeping:

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Weeping occurs at low vapor/gas flow rates. The upward vapor flow through the plate perforations
prevents the liquid from leaking through the tray perforation. At low vapor flow rates, liquid start to
leak/rain through the perforation (called weeping). When none of the liquid reaches the downcomer
at extreme weeping condition at very low vapor flow rate, it is called dumping. The weeping
tendency increases with increasing fractional whole area and liquid flow rates. The vapor velocity at
the weep point (where liquid leakage through holes starts) is the minimum value for stable operation.
For a chosen hole area, the minimum operating vapour flow velocity ( ,) at minimum flow rate
for stable operation should be above weep point vapor velocity. The minimum vapor velocity (min )
at the weep point
----3
Where, = hole diameter, mm,
= vapor density, kg/m3 (maximum value of vapor density)
= constant (2) of weep-point correlation depends on the depth of clear liquid
(Weir crest + weir height) on the plate
Weir crest () can be determined using the Francis weir correlation:
----4
=weir length, m
=liquid flow rate over the crest, kg/s
= liquid density, kg/m3
Actual operating minimum vapor velocity:
----5
To avoid weeping: Umin, op > Umin
Liquid entrainment:
Entrainment is the phenomena in which liquid droplets are carried by vapor/gas to the tray above.
Therefore, the less volatile liquid components from bottom tray are mixed with liquid having
relatively more volatile materials on the overhead tray. It counteracts the desired mass transfer
operation and the plate efficiency decreases. Entrainment increases with vapor velocity. The
fractional entrainment 6, can be predicted using fairs correlation in terms of the flow parameter and
actual flooding velocity
----6
Effect of on Murphree plate efficiency can be estimated using Colburn equation
Emv
Ea
Emv
1
1
----7
= Murphree vapor efficiency
E= Corrected Murphree vapor efficiency for liquid entrainment

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Tray hydraulic parameters:

Total plate pressure drop:
All gas pressure drops () are expressed as heads of the clear liquid and is given by:
= + + + ----8
Where, =dry plate pressure drop, mm
=height of liquid over weir (weir crest), mm
=weir height, mm
=residual head, mm
Dry plate pressure drop ():
Dry plate pressure drop occurs due to friction within dry short holes. can be calculated using
following expression derived for flow through orifices
----9
Maximum vapor velocity:
Ah
Ap
The orifice coefficient, C0 can be determined in terms of

and

----10
Platethickness
holediamet er

Residual gas pressure head hr:

The residual pressure drop results mainly from the surface tension as the gas releases from a
perforation. The following simple equation can be used to estimate hr with reasonable accuracy
Downcomer backup (

----11
and downcomer residence time:

The liquid level and froth in the downcomer should be well below the top of the outlet weir on the
tray above to avoid flooding
b = (w + ) +dc + t ----12
Head loss in downcomer:
----13
Lwd = Downcomer liquid flow rate, kg/s
Am= Smaller of clearance area under the downcomer apron (Ap) and downcomer area (Ad)
The average density of aerated liquid in the downcomer can be assumed as 0.5 of the clear liquid
density. Therefore, half of the sum of the plate spacing and weir height should be greater than the
downcomer backup.

Downcomer residence time () should be sufficient for the disengagement of liquid and vapor in the
downcomer to minimize entrained vapor. The value of >3 s is suggested.

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=clear liquid back up, mm

Column sizing approximation
The column sizing is a trial and error calculation procedure, starting with a tentative tray layout. The
calculation is then revised until an acceptable design is obtained subject to satisfying the tray
pressure drop, weeping, flooding and liquid entrainment limits. The column sizing is carried at the
tray where the anticipated column loading is the highest and lowest for each section. However, the
vapor flow rates have the highest impact on tower diameter. For an example, the sizing calculation is
performed on the top tray for the above feed section and on the bottom tray for below feed section,
for a single feed distillation column with one top and one bottom product. The tray spacing
determines the column height. Lower tray spacing is desirable to minimize construction cost by
checking against the column performance criteria. The suggested tray spacing () with column
diameter is appended below. The detailed column sizing calculations are discussed in the solved
example.
Tower diameter, m
1 or less
1-3
3-4
4-8

Tray spacing, mm
500 (150 mm is minimum)
600
750
900

Column diameter
The column diameter is determined from the flooding correlation for a chosen plate spacing. The
superficial vapor/gas velocity () at flooding through the net area relates to liquid and vapor
densities according to Fairs correlation . is an empirical constant, depends on tray spacing and
can be estimated against the flow parameter () based on mass flow rate of liquid () and vapor
().
Typically, the design velocity () through the net area is about 80 to 85% of for non-foaming
liquids and 75% or less for foaming liquid depending on allowable plate pressure drop and
entrainment. It is a common practice to have uniform tower diameter in all sections of the column
even though the vapor/gas and liquid loadings are expected to be different to minimize the cost of
construction. The uniformity in tower diameter may require selecting different plate spacing in
different sections of the tower.
Hole diameter, hole pitch and plate thickness:
The plate hole diameters (dh) from 3 to 12 mm are commonly used. The bigger sizes are susceptible
to weeping. The holes may be drilled or punched and the plate is fabricated from stainless steel and
other alloys than carbon steel. The centre to centre distance between two adjacent holes is called hole
pitch ( . Perforations can be arranged in square or equilateral triangular arrays with respect to the
vapor/gas flow direction. The normal range of is from 2.5 to 5 times of dh

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Ah

Ap
For triangular pitch:

.907(dh/Ip)2

Plate thickness (tt) typically varies from 0.2 to 1.2 times of the hole diameter and should be verified
by checking the allowable plate pressure drop.
Weir heightand weir length
The depth of liquid on the tray is maintained by installing a vertical flat plate, called weir. Higher
weir height (hw ) increases the plate efficiency. But it increases plate pressure drop, entrainment rate
and weeping tendency. Weir heights from 40 to 90 mm are common in applications for the columns
operating above the atmospheric pressure. For vacuum operation, hw =6 to 12 mm are
recommended. The weir length (Lw) determines the downcomer area. A weir length of 60 to 80% of
tower diameter is normally used with segmental downcomers. The dependency of Lw on downcomer
Ad
Aa
area is calculated against the percentage value of
.
Calming zones
Two blank areas called calming zone, are provided between the inlet downcomer or inlet weir and
the perforation area, and also between the outlet weir and perforation area. Inlet calming zone helps
in reducing excessive weeping in this area because of high vertical velocity of the entering liquid in
the downward direction. Outlet calming zone allows disengagement of vapor before the liquid enters
the downcomer area. A calming zone between 50 to 100mm is suggested.
Acknowledgement and Conclusion:
Nanoemulsion is extremely useful in the fields of mass transfer where it replaces the conventional
absorbent, biochemical engineering, it is used in the diagnostics and various other fields, it is to bring
a revolution by substituting various other conventional materials. I thank the faculty members of
Chemical engineering department, RVCE for giving me an opportunity to understand and gain
tremendous knowledge in the above topic.
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