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RASHTREEYA VIDYALAYA COLLEGE OF ENGINEERING

Development of Nanoemulsion by emulsification evaporation technique

1) Ashwanth Subramanian1

Rashtreeya Vidyalaya College of Engineering, Bangalore [email protected]

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 µm. 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 bi-continuous. 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

DEPARTMENT OF CHEMICAL ENGINEERING

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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 in new biotechnological devices. To answer the variability of conditions encountered by the different


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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 bio-nanotechnologies. 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.

Specific Capture and Detection of the Nucleic Acid Target (ELOSA):

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


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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. baumannii’s low permeability of the outer membrane, its ability to acquire genetic elements efficiently, and its ability to establish biofilms have made treatment options limited.


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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 diluted 10- to 100-fold in water, resulting in a stable final product. The dilute emulsions are milky in


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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 ingredients and thus increase their concentration in the skin. Another advantage is the small-sized


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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 trans-epidermal 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 <=106µmwhich 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 microbial disinfectants require large doses of their respective active ingredients to surround pathogen


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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-ìm 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. Nanoemulsion formulations for improved oral delivery of poorly soluble drug. 7. Self-nanoemulsifying drug delivery systems. 8. Nanoemulsions as a vehicle for transdermal delivery. 9. 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. NANOTECHNOLOGY—PREPARATION 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 θ 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 Stokes-Einstein Equation:

D= k∗T

6∗∏ ¿R∗η

Where k is the Boltzmann-Constant, T the temperature and η 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 Γ 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 He–Ne 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.

𝐴𝑏𝑠𝑜𝑟𝑏𝑒𝑛𝑡𝑆𝑜𝑙𝑢𝑡𝑒 +𝐶𝑎𝑟𝑟𝑖𝑒𝑟 𝑔𝑎𝑠 → 𝑆𝑜𝑙𝑢𝑡𝑒 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑑 𝑖𝑛 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑛𝑡 +𝐶𝑎𝑟𝑟𝑖𝑒𝑟 𝑔𝑎𝑠Single-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 processThe overall material balance for a countercurrent absorption process is

Lb + VT = Lt + Vb ----1Where 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


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Where yA = mole fraction of A in the vapor phase xA = mole fraction of A in the liquid phaseFor 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

carrier gas and solvent rates remain constant throughout the absorber. Using L to denote the flow

rate of the nonvolatile and V to denote the carrier gas flow rate, the material balance for solute A becomes

----4Or

----5The 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

----7In 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 Henry’s 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/vapor-liquid) 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 cross-flow plates are most widely practiced and the three main types of cross flow plates are: bubble cap, valve and sieve trays with downcomer.


18


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 capsValve 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 traySieve 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

Capacity Efficiency Pressure drop

Entrainment Turndownratio

Cost

Bubble cap

Mediumhigh

Mediumhigh

High ~3 times thansieve tray

Excellent 100-200 % more than sievetray

Valve High tovery high

High Medium to high

Medium 4 to 10.1 20-50% morethan sieve tray

Sieve High High Medium Medium 2.1 Cheapest of all


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

The centrifugal absorber:

In an attempt to obtain the benefits 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 first ring, splashes over to the baffle 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 flow, or at the bottom if counter-current flow 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 AbsorberSpray 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 film 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 humidifiers, 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


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V. CEDD---PLATE COLUMN ABSORPTION TOWER DESIGN

General Design Procedure:

1. Calculate the maximum and minimum vapour and liquid flow-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 flooding considerations . 5. Decide the liquid flow 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 flooding based on chosen column diameter.12. Check entrainment, if too high return to step 4 . 13. Optimise design: repeat steps 3 to 12 to find smallest diameter and plate spacing acceptable (lowest cost). 14. Finalise design: draw up the plate specification 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 fair’s correlation:

----1𝜌𝑣 = vapor density, kg/m3𝜌𝑙 = liquid density, kg/m3 σ = liquid surface tension, mN/m (dyn/cm)𝐶𝑠𝑏𝑓= capacity parameter (m/s) can be calculated in terms of plate spacing and flow parameter:

----2𝐿 =liquid flow rate, kg/s 𝑉 =vapor flow rate, kg/s The design gas velocities (𝑈𝑛) is generally 80-85% of 𝑈𝑛𝑓 for non-foaming liquids and 75% or less for foaming liquids subject to acceptable entrainment and plate pressure drop.


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Sieve tray weeping:

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 (𝑈𝑚𝑖 ,𝑝) at minimum flow rate for stable operation should be above weep point vapor velocity. The minimum vapor velocity (𝑈min

) at the weep point

----3Where, 𝑑ℎ= hole diameter, mm, 𝜌𝑣 = vapor density, kg/m3 (maximum value of vapor density) 𝐾𝟐 = constant (𝐾2) of weep-point correlation depends on the depth of clear liquid (Weir crest + weir height) on the plate

Weir crest (ℎ𝑤𝑐) can be determined using the Francis’ weir correlation:

----4𝐿𝑊𝐶=weir length, m 𝐿𝑊=liquid flow rate over the crest, kg/s 𝜌𝑙 = 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 fair’s correlation in terms of the flow parameter and actual flooding velocity

----6Effect of 𝛹 on Murphree plate efficiency can be estimated using Colburn equation

Ea= Emv

1+ψ Emv1−ψ ----7

𝐸𝑚𝑣 = Murphree vapor efficiency


24


E𝑎= Corrected Murphree vapor efficiency for liquid entrainment

Tray hydraulic parameters: Total plate pressure drop:All gas pressure drops (ℎ𝑡) are expressed as heads of the clear liquid and ℎ𝑡is given by: ℎ𝑡 = ℎ𝑑 + ℎ𝑤𝑐 +ℎ𝑤 + ℎ𝑟 ----8Where, ℎ𝑑 =dry plate pressure drop, mm ℎ𝑤𝑐 =height of liquid over weir (weir crest), mm ℎ𝑤 =weir height, mm ℎ𝑟 =residual head, mm

Dry plate pressure drop (𝒉𝒅):

Dry plate pressure drop occurs due to friction within dry short holes. ℎ𝑑 can be calculated using following expression derived for flow through orifices

----9Maximum vapor velocity:

----10

The orifice coefficient, C0 can be determined in terms of

AhAp and

Platethicknessholediameter

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

----11Downcomer backup ( 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 ℎb = (ℎw + ℎ𝑤𝑐) +ℎdc + ℎt ----12Head 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.


25


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

ℎ𝑏𝑐 =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 (𝑇𝑡) with column diameter is appended below. The detailed column sizing calculations are discussed in the solved example.

Tower diameter, m Tray spacing, mm

1 or less 500 (150 mm is minimum)1-3 6003-4 750

4-8 900

Column diameter

The column diameter is determined from the flooding correlation for a chosen plate spacing. The superficial vapor/gas velocity (𝑈𝑛𝑓) at flooding through the net area relates to liquid and vapor densities according to Fair’s correlation .𝐶𝑠𝑏𝑓 is an empirical constant, depends on tray spacing and can be estimated against the flow parameter (𝐹𝐿𝐺) based on mass flow rate of liquid (𝐿) and vapor (𝑉).Typically, the design velocity (𝑈𝑛) through the net area is about 80 to 85% of 𝑈𝑛𝑓 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


26


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

For triangular pitch:

AhAp

=.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

area is calculated against the percentage value of

AdAa .

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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