Ultrasonic Production of Stable Nanoemulsions

  • Nanoemulsionsalso known as miniemulsions or submicron emulsionsare used in a wide range of applications in chemistry, paints, coatings, cosmetics, pharmaceuticals and food.
  • Ultrasonicators are known as a highly efficient and reliable technique for the production of long-term stable nanoemulsions.

Why Ultrasonics for Nanoemulsification

Ultrasonic nanoemulsification is a technique that utilizes low-frequency, high-power ultrasound waves to create stable and uniform emulsions of tiny droplets, typically in the range of 10-200 nm. This technique has several advantages over traditional emulsification methods, which make it superior in various applications. Some of these advantages are:

  • Uniform particle size: Ultrasonic nanoemulsification produces small and uniform droplets, which offer better stability and bioavailability. These droplets have a high surface area to volume ratio, making them more reactive and effective in various applications.
  • High stability: Ultrasonic nanoemulsions have a high kinetic stability due to their small size and uniformity, which makes them resistant to coalescence, flocculation, and sedimentation. This stability makes them ideal for use in food, pharmaceuticals, cosmetic and chemical applications.
  • Reduced energy consumption: Ultrasonic nanoemulsification requires lower energy input than traditional emulsification methods such as homogenization or microfluidization, making it more energy-efficient and cost-effective.
  • Versatility: Ultrasonic nanoemulsification can be used to emulsify a wide range of materials, including lipids, hydrophilic compounds, and water-insoluble substances. This makes it a versatile technique that can be used in various applications.
    Fast processing time: Ultrasonic nanoemulsification is a fast process that can be completed in minutes, making it suitable for large-scale production.

Overall, ultrasonic nanoemulsification offers several advantages over traditional emulsification methods, making it a superior technique for various applications.
 

n this video we make a nano-emulsion of CBD rich hemp oil in water using a Hielscher UP400St ultrasonicator. We then measure the nano-emulsion using a NANO-flex DLS. The measurement results show a very narrow, volume-weighed particle size distribution in the range from 9 to 40 nanometers. 95 percent of all particles are below 28 nanometers.

CBD Nanoemulsion - Produce a translucent nano-emulsion using a UP400St ultrasonic homogenizer!

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અમારી નોંધ કરો ગોપનીયતા નીતિ.


Ultrasonic preparation of a CBD nano-emulsion using the UP400ST ultrasonic probe.

Ultrasonic preparation of a clear nano-emulsion using the UP400ST ultrasonicator.

Ultrasonic Formation of Nanoemulsions

Ultrasonic emulsification is caused by coupling the waves of power ultrasound into a liquid system. By sonicating a liquid, two mechanisms occur:

  1. The acoustic field generates waves that travel through the liquid and cause microturbulences and an interfacial movement. Thereby, the boundary phase becomes unstable, so that the dispersed (internal) phase eventually breaks and forms droplets in the continuous (external) phase.
  2. The application of low-frequency, high power ultrasonics generates cavitation (Kentish et al. 2008). By ultrasonic cavitation, microbubbles or voids are formed in the medium due to the pressure cycles of the ultrasound wave. The microbubbles / voids grow over several wave cycles until they collapse violently. This bubble implosion causes locally extreme conditions such as very high shear, liquid jets, and extreme heating and cooling rates. (Suslick 1999).

These extreme forces break primary droplets of dispersed (internal) phase down to nanosize droplet and mix them homogeneously into the continuous (external) phase.
Read here more about the effects of ultrasonic cavitation on emulsification!

Pharmaceutical Nanoemulsions

Lipid miniemulsionsproduced by ultrasonicsare widely applied as carrier for pharmacological agents in pharmaceutical formulations. For instance, miniemulsions can act as parenteral drug carrier or drug delivery device to target tissues. Besides of the high bioavailability of the encapsulated active compounds, the advantages of miniemulsions lie in their high biocompatibility, biodegradability, stability, and ease of large-scale production. Due to their structural properties, they can incorporate hydrophobic as well as amphipathic molecules. Ultrasonically prepared nanoemulsions have been loaded with tocopherols, vitamins, curcurmin and many other pharmacological substances.
Hielscher’s ultrasonic systems are reliable emulsifiers for the preparation of drug-loded nanoemulsions. For the ultrasonic emulsification, Hielscher offers various accessories to optimize the emulsifying process. Hielschers MultiPhaseCavitator is an unique add-on for ultrasonic flow cells, where the second phase is injected as very narrow stream directly into the ultrasonic hot spot zone of emulsification.

Ultrasonic preparation of nanosuspensions is an efficacious technique for the production of pharmaceutical formulations with increased bioavailability.

Ultrasonicator UP400ST for the formulation of pharmaceutical nanosuspensions with increased bioavailbility.

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Ultrasonic Nano-Emulsions: This video demonstrated the rapid production of a nano-emulsion of oil in water. The UP200Ht homogenizes the oil and water in seconds.

Ultrasonic Emulsifying with UP200Ht with S26d14 probe

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Food-Grade Nanoemulsions

Nanoemulsions offer various benefits for the formulation of food products. Nanoemulsions show a good stability to gravitational separation, flocculation, coalescence, and offer controlled release and/or absorption of functional ingredients due to their small droplet size and large surface area. Additionally, they offer a high bioavailability of active compounds which is important for the delivery of nutrients and active substances. Furthermore, they offer good formulation properties since they are transparent or visually translucent and their submicron- / nano-size droplets cause a smooth and creamy mouth feel. Thereby, the production of stable nano-emulsions is an omnipresent task for the food industry, e.g. to formulate vitamin or fatty acid fortified products (e.g. vitamin C, vitamin E omega-3, omega-6, omega-9 derived from plant seed or fish oil) or to produce flavoured products (e.g. with essential oils).

Droplet distribution measurement of an ultrasonically dispersed nano-emulsion.

Nanosized droplet distribution of an ultrasonically dispersed nanoemulsion (lavender oil-in-water emulsion). Emulsion was prepared with the ultrasonic probe UP400St.

Cosmetic Nanoemulsions

Especially water-in-oil (W/O) nanoemulsions offer various benefits for the encapsulation of bioactive hydrophilic substance into nanoscale droplets (in single or double emulsions).
Click here to read more about the surfactant-free formulation of cosmetic emulsions with ultrasonics!

Miniemulsion Polymerization

Ultrasonically assisted miniemulsion polymerization is applied to various processesfrom the encapsulation of inorganic particles to the synthesis of latex particles. The application of power ultrasound to chemical reactions such as polymerization, synthesis etc. are known as sonochemistry.
Click here to read more about સોનોકેમિસ્ટ્રી, ultrasonic synthesis of latex અને ultrasonic precipitation!

Emulsion Stabilization

Although some nanoemulsions can be shelf stable without the use of any surfactants or emulsifiers due to the nano-scaled droplet size and distribution, other nanoemulsions require the use of stabilizing agents to obtain long-term stability and optimal product quality. Stabilization can be accomplished by adding either surfactants (tensids) or solid particles which act as stabilizers. Emulsions, which are stabilized by solid particles are known as Pickering emulsions. Lactose, albumin, lecithin, chitosan, cyclodextrin, maltodextrin, starch etc. can be used as colloidal stabilizers in Pickering emulsions. Click here to learn more about ultrasonically generated Pickering emulsions!
Ultrasonic emulsification can be performed for all types of emulsions. If a stabilizing agent is required for a specific emulsion, can be easily tested in small scale.
Please note that the amount of required surfactant increases with a decreasing droplet size since the surface-area-to-volume ratio (S/V) for spheres is given by: S/V = 3/R. For example, the smaller the diameter of a particle or droplet, the more surface area it has relative to its volume.

Ultrasonic Emulsification Equipment

The production of stable submicron- and nano-emulsions requires powerful ultrasonic equipment. Hielscher ultrasonic emulsification equipment delivers very high amplitudes (up to 200µm for industrial ultrasonicators, higher amplitudes on request) to generate an intense acoustic field.
However, for the production of stable nanoemulsions, power ultrasound equipment alone is often not sufficient. Besides sufficient ultrasonic power, precise control of the process parameters, and sophisticated accessories (such as sonotrodes, flow cell reactors, cooling) are necessary to obtain nano-sized droplets and a homogeneous dispersion of both, the aqueous and oil phase into each other.
Hielscher MultiPhaseCavitator: In order to produce superior emulsions with a very narrow droplet distribution, Hielscher has developed a unique flow cell insertthe MultiPhaseCavitator. With this special flow cell add-on, the second phase of the emulsion is continuously injected via 48 small cannulas into the cavitation zone. This technology allows for the reliable and efficacious production very small nano-size droplets and highly stable emulsions.

Hielscher Ultrasonics is specialized in supplying superior ultrasonic systems and accessories for optimum processing results. Our long-term experience in ultrasonic processing and our close cooperation with our clients ensures the successful implementation of ultrasonics into production lines.
For initial tests, process development and process optimization, we offer a fully equipped process lab and technical center.
Furthermore, we offer in-depth consulting, the development of customized ultrasonic systems and profound technical service for installation, training, and maintenance.

The video shows the highly efficient emulsification of oil. The ultrasonic processor used is a Hielscher UP400St ultrasonicator, which is ideal to prepare medium size batches of high-quality emulsions.

Make Stable Nanoemulsions with the Hielscher Ultrasonics UP400St (400 Watts)

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નીચે આપેલ કોષ્ટક તમને અમારા અલ્ટ્રાસોનિકેટર્સની અંદાજિત પ્રોસેસિંગ ક્ષમતાનો સંકેત આપે છે:

બેચ વોલ્યુમપ્રવાહ દરભલામણ કરેલ ઉપકરણો
0.5 to 1.5mLnaVialTweeter
1 થી 500 મિલી10 થી 200 એમએલ/મિનિટUP100H
10 થી 2000 એમએલ20 થી 400 એમએલ/મિનિટUP200Ht, UP400St
0.1 થી 20L0.2 થી 4L/મિનિટUIP2000hdT
10 થી 100 લિ2 થી 10L/મિનિટUIP4000hdT
15 to 150L3 to 15L/minUIP6000hdT
na10 થી 100L/મિનિટUIP16000
naમોટાનું ક્લસ્ટર UIP16000

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This video demonstrates the Hielscher ultrasonic processor UP400S preparing a nano-sized vegetable oil-in-water emulsion.

Emulsifying of Vegetable Oil in Water using the UP400S

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Facts Worth Knowing

Emulsions, Droplet Size, and Surfactants

Emulsions are defined as two immiscible liquids: One of the liquidsthe so-called dispersed or internal phaseis dispersed as spherical droplets within the other liquid, known as continuous or external phase. The most prominent liquids used to form an emulsion are oil and water. When the oil phase is dispersed in the water/aqueous phase, the system is an oil-in-water emulsion, whilst when the water/aqueous phase is dispersed in the oil phase, it is a water-in-oil emulsion. Emulsions are distinguished respectively their particle size and thermodynamic stability as macroemulsions, microemulsions, and nanoemulsions, respectively.

Nanoemulsions

Nanoemulsions are nanoparticulate dispersions, which consist in nano-sized droplets. The high shear forces of power ultrasound rupture the droplets so that they are reduced to submicron and nano diameter. Generally, smaller droplet sizes lead to greater emulsion stability. Nanoemulsions can be distinguished as O/W (oil-in-water), W/O (water-in-oil) or as multiple/double emulsions such as W/O/W and O/W/O. Nanoemulsion are transparent or even translucent (in the visible spectrum) depending on the consistency and droplet size. Nanoemulsions are generally defined by a droplet size between 20 and 200nm. With a descending droplet size, the emulsion’s propensity for coalescence is decreasing (decreasing Ostwald ripening).
Nanomaterials and nanoemulsions are characterized by physical properties that differ from microemulsions. Nano-sized particles show either completely different properties or their typical properties are expressed in a very extreme form. The visible appearance of nanoemulsions have a different appearance than micron-sized emulsions since the droplets are too small to interfere with the optical wavelengths of the visible spectrum. Therefore nanoemulsions exhibit very little light scattering and appear transparent or optically translucent.
The droplet size of an emulsion is influenced by the composition of the oil phase, the interfacial properties and viscosity of both, the continuous and dispersed phases, the type emulsifier/surfactant, shear rate during emulsification, as well as the solubility of the oil phase in water.
Nanoemulsions are widely used in diverse applications such as drug delivery, food & beverages, cosmetics, pharmaceuticals, and material science & synthesis.

Surfactants

Emulsifiers are an essential factor to prepare a stable emulsion / nanoemulsion. Emulsifiers are surface-active agents that form a protective layer about the droplet and reduce the interfacial tension, thereby preventing Ostwald ripening, coalescence, and creaming.
Types of surfactants:

  • Small molecule surfactants: Non-ionic emulsifier such as Tween and Span show a low toxicity and irritancy when administered orally, parenterally and dermally and are therefore preferred over ionic emulsifiers. Tween and Span are the preferred stabilizers for emulsion formulations in the food, pharmaceutical and cosmectic industry.
    Tweens: Tween 20/60/80 are known as polysorbate 20/60/80 (PEG-20 dehydrated sorbierite monolaurate, PEG-20 dehydrated sorbierite monostearate, polyoxyethylene sorbitan monooleate). They are nonionic surfactants / emulsifiers derived from sorbitol. They easily dissolves in water, ethanol, methanol or ethyl acetate, but only a little in mineral oil.
    Spans: Span20/40/60/80 are sorbitan fatty acid esters / sorbitan esters, which are non-ionic surfactants with emulsifying, dispersing, and wetting properties. Span surfactants are produced by the dehydration of sorbitol.
  • Phospholipids: egg yolk, soy or dairy lecithin
  • Amphiphilic proteins: Whey protein isolate, caseinate
  • Amphiphilic polysaccharides: gum arabic, modified starches

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High performance ultrasonics! Hielscher's product range covers the full spectrum from the compact lab ultrasonicator over bench-top units to full-industrial ultrasonic systems.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers from lab to industrial size.


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