Miniemulsion

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A miniemulsion (also known as nanoemulsion) is a particular type of emulsion. A miniemulsion is obtained by ultrasonicating a mixture comprising two immiscible liquid phases (for example, oil and water), one or more surfactants and, possibly, one or more co-surfactants (typical examples are hexadecane or cetyl alcohol). They usually have nanodroplets with uniform size distribution (20–500 nm) and are also known as sub-micron, mini-, and ultra-fine grain emulsions. [1]

Contents

Schematic illustration of nanoemulsion structure, including the biphasic systems (O/W or W/O), in which an appropriate volume of the internal oil phase is disseminated in the bulk aqueous solution or vice versa; and the multiple systems (W/O/W or O/W/O), within a single system, the inner water phase is dispersed in an oil phase, which is then dispersed in a bulk aqueous phase or vice versa. 1-s2.0-S0168365922006307-gr1 lrg.jpg
Schematic illustration of nanoemulsion structure, including the biphasic systems (O/W or W/O), in which an appropriate volume of the internal oil phase is disseminated in the bulk aqueous solution or vice versa; and the multiple systems (W/O/W or O/W/O), within a single system, the inner water phase is dispersed in an oil phase, which is then dispersed in a bulk aqueous phase or vice versa.

How to prepare a miniemulsion

  1. Selection of ingredients: The first step in creating a nanoemulsion is to select the ingredients, which include the oil, water, and emulsifying agent. The type and proportions of these ingredients will affect the stability and properties of the final emulsion. [3]
  2. Preparation of oil and aqueous phases: The oil and water phases are separately prepared, with any desired ingredients, such as surfactants or flavoring agents, added at this step.
  3. Mixing oil and emulsifier with stirrer: Next, the oil and water phases are mixed in the presence of an emulsifying agent, typically using a high-shear mixing device such as a homogenizer or a high-pressure homogenizer. [4]
  4. Aging and stabilization: The emulsion is typically aged at room temperature to allow the droplets to stabilize, after which it can be cooled or heated as required. [4]
  5. Optimizing and characterization: The droplet size and stability are then optimized by adjusting the ingredients and process parameters, such as temperature, pH, and mixing conditions. The nanoemulsion is also sterilized by filtration with 0.22μm. Several methods, such as DLS, TEM, and SEM, can characterize the final nanoemulsion's properties. [5]
  6. Analyzing the quality of the particle sizer
IUPAC definition

Mini-emulsion: emulsion in which the particles of the dispersed phase have diameters in the range from approximately 50 nm to 1 μm.

Note 1: Mini-emulsions are usually stabilized against diffusion degradation (Ostwald ripening (ref. [6] )) by a compound insoluble in the continuous phase.

Note 2: The dispersed phase contains mixed stabilizers, e.g., an ionic surfactant, such as sodium dodecyl sulfate (n-dodecyl sulfate sodium) and a short aliphatic chain alcohol ("co-surfactant") for colloidal stability, or a water-insoluble compound, such as a hydrocarbon ("co-stabilizer" frequently and improperly called a "co-surfactant") limiting diffusion degradation. Mini-emulsions are usually stable for at least several days. [7]

Mini-emulsion polymerization: Polymerization of a mini-emulsion of monomer in which all of the polymerization occurs within preexisting monomer particles without the formation of new particles. [8]

Methods of preparing nanoemulsions/miniemulsions

There are two general types of methods for preparing miniemulsions:

Miniemulsions are kinetically stable but thermodynamically unstable. [13] Oil and water are incompatible in nature, and the interface between them is not favored. Therefore, given a sufficient amount of time, the oil and water in miniemulsions separate again. Various mechanisms such as gravitational separation, flocculation, coalescence, and Ostwald ripening result in instability. [14] In an ideal miniemulsion system, coalescence and Ostwald ripening are suppressed thanks to the presence of the surfactant and co-surfactant. [9] With the addition of surfactants, stable droplets are then obtained, which have typically a size between 50 and 500 nm. [15] [16]

Instruments needed in Nanoemulsions

Sterile filter

A sterile filter is a device used to remove microorganisms and other contaminants from a liquid or gas, making it sterile. [17] [18] Sterile filters are commonly used in the medical, pharmaceutical, and biotech industries to ensure that the products produced are free of bacteria and other harmful organisms.

There are different types of filters which include:

Nanogenizer

A nanogenizer, also known as a high-pressure homogenizer or a microfluidizer, is a device used to create small droplets or particles by applying high pressure to a liquid mixture. [24] These devices can be used to produce nanoemulsions, as well as other types of emulsions and suspensions. [25] They work by passing the mixture through a small orifice under high pressure, which causes the liquid to be sheared and broken into small droplets or particles. The size of the droplets or particles can be controlled by adjusting the pressure and the design of the orifice. [26]

Nanoparticle sizer

The dual-light particle analyzer Non particle analyzer.png
The dual-light particle analyzer

A nanoparticle sizer, also known as a nanoparticle analyzer, is a device used to measure the size, size distribution, and concentration of nanoparticles in a sample. [27] [28] The size of nanoparticles is typically in the range of 1 to 100 nanometers (nm), and they are much smaller than the particles that can be measured with conventional particle size analyzers. [29]

Applications

Miniemulsions have wide application in the synthesis of nanomaterials and in the pharmaceutical and food industries. [30] [31] For example, miniemulsion-based processes are, therefore, particularly adapted for the generation of nanomaterials. There is a fundamental difference between traditional emulsion polymerisation and a miniemulsion polymerisation. Particle formation in the former is a mixture of micellar and homogeneous nucleation, particles formed via miniemulsion however are mainly formed by droplet nucleation. In the pharmaceutical industry, oil droplets act as tiny containers that carry water-insoluble drugs, and the water provides a mild environment that is compatible with the human body. [32] [33] Moreover, nanoemulsions that carry drugs allow the drugs to crystallize in a controlled size with a good dissolution rate. [34] [35] Finally, in the food industry, miniemulsions can not only be loaded with water-insoluble nutrients, such as beta-carotene and curcumin, but also improve the nutrients' digestibility. [12] Miniemulsions are also used in the creation of cannabinoid infused beverages and foods. Emulsifying cannabiniods has shown to increase bioavailability and digestion time. [36]

Related Research Articles

An emulsion is a mixture of two or more liquids that are normally immiscible owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although the terms colloid and emulsion are sometimes used interchangeably, emulsion should be used when both phases, dispersed and continuous, are liquids. In an emulsion, one liquid is dispersed in the other. Examples of emulsions include vinaigrettes, homogenized milk, liquid biomolecular condensates, and some cutting fluids for metal working.

In polymer chemistry, emulsion polymerization is a type of radical polymerization that usually starts with an emulsion incorporating water, monomers, and surfactants. The most common type of emulsion polymerization is an oil-in-water emulsion, in which droplets of monomer are emulsified in a continuous phase of water. Water-soluble polymers, such as certain polyvinyl alcohols or hydroxyethyl celluloses, can also be used to act as emulsifiers/stabilizers. The name "emulsion polymerization" is a misnomer that arises from a historical misconception. Rather than occurring in emulsion droplets, polymerization takes place in the latex/colloid particles that form spontaneously in the first few minutes of the process. These latex particles are typically 100 nm in size, and are made of many individual polymer chains. The particles are prevented from coagulating with each other because each particle is surrounded by the surfactant ('soap'); the charge on the surfactant repels other particles electrostatically. When water-soluble polymers are used as stabilizers instead of soap, the repulsion between particles arises because these water-soluble polymers form a 'hairy layer' around a particle that repels other particles, because pushing particles together would involve compressing these chains.

<span class="mw-page-title-main">Flocculation</span> Process by which colloidal particles come out of suspension to precipitate as floc or flake

In colloidal chemistry, flocculation is a process by which colloidal particles come out of suspension to sediment in the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The action differs from precipitation in that, prior to flocculation, colloids are merely suspended, under the form of a stable dispersion and are not truly dissolved in solution.

<span class="mw-page-title-main">Electrospinning</span> Fiber production method

Electrospinning is a fiber production method that uses electric force to draw charged threads of polymer solutions or polymer melts up to fiber diameters in the order of some hundred nanometers. Electrospinning shares characteristics of both electrospraying and conventional solution dry spinning of fibers. The process does not require the use of coagulation chemistry or high temperatures to produce solid threads from solution. This makes the process particularly suited to the production of fibers using large and complex molecules. Electrospinning from molten precursors is also practiced; this method ensures that no solvent can be carried over into the final product.

Microemulsions are clear, thermodynamically stable isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. The aqueous phase may contain salt(s) and/or other ingredients, and the "oil" may actually be a complex mixture of different hydrocarbons. In contrast to ordinary emulsions, microemulsions form upon simple mixing of the components and do not require the high shear conditions generally used in the formation of ordinary emulsions. The three basic types of microemulsions are direct, reversed and bicontinuous.

A dispersant or a dispersing agent is a substance, typically a surfactant, that is added to a suspension of solid or liquid particles in a liquid to improve the separation of the particles and to prevent their settling or clumping.

<span class="mw-page-title-main">Ouzo effect</span> Phenomenon observed in drink mixing

The ouzo effect, also known as the louche effect and spontaneous emulsification, is the phenomenon of formation of a milky oil-in-water emulsion when water is added to ouzo and other anise-flavored liqueurs and spirits, such as pastis, rakı, arak, sambuca and absinthe. Such emulsions occur with only minimal mixing and are highly stable.

A Ramsden emulsion, sometimes named Pickering emulsion, is an emulsion that is stabilized by solid particles which adsorb onto the interface between the water and oil phases. Typically, the emulsions are either water-in-oil or oil-in-water emulsions, but other more complex systems such as water-in-water, oil-in-oil, water-in-oil-in-water, and oil-in-water-in-oil also do exist. Pickering emulsions were named after S.U. Pickering, who described the phenomenon in 1907, although the effect was first recognized by Walter Ramsden in 1903.

<span class="mw-page-title-main">Janus particles</span> Type of nanoparticle or microparticle

Janus particles are special types of nanoparticles or microparticles whose surfaces have two or more distinct physical properties. This unique surface of Janus particles allows two different types of chemistry to occur on the same particle. The simplest case of a Janus particle is achieved by dividing the particle into two distinct parts, each of them either made of a different material, or bearing different functional groups. For example, a Janus particle may have one half of its surface composed of hydrophilic groups and the other half hydrophobic groups, the particles might have two surfaces of different color, fluorescence, or magnetic properties. This gives these particles unique properties related to their asymmetric structure and/or functionalization.

<span class="mw-page-title-main">Emulsion dispersion</span> Thermoplastics or elastomers suspended in a liquid state by means of emulsifiers

An emulsion dispersion is thermoplastics or elastomers suspended in a liquid state by means of emulsifiers.

<span class="mw-page-title-main">Solid lipid nanoparticle</span> Novel drug delivery system

Lipid nanoparticles (LNPs) are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were first approved in 2018 for the siRNA drug Onpattro. LNPs became more widely known in late 2020, as some COVID-19 vaccines that use RNA vaccine technology coat the fragile mRNA strands with PEGylated lipid nanoparticles as their delivery vehicle.

<span class="mw-page-title-main">Membrane emulsification</span>

Membrane emulsification (ME) is a relatively novel technique for producing all types of single and multiple emulsions for DDS, solid micro carriers for encapsulation of drug or nutrient, solder particles for surface-mount technology, mono dispersed polymer microspheres. Membrane emulsification was introduced by Nakashima and Shimizu in the late 1980s in Japan.

Macroemulsions are dispersed liquid-liquid, thermodynamically unstable systems with particle sizes ranging from 1 to 100 μm, which, most often, do not form spontaneously. Macroemulsions scatter light effectively and therefore appear milky, because their droplets are greater than a wavelength of light. They are part of a larger family of emulsions along with miniemulsions. As with all emulsions, one phase serves as the dispersing agent. It is often called the continuous or outer phase. The remaining phase(s) are disperse or inner phase(s), because the liquid droplets are finely distributed amongst the larger continuous phase droplets. This type of emulsion is thermodynamically unstable, but can be stabilized for a period of time with applications of kinetic energy. Surfactants are used to reduce the interfacial tension between the two phases, and induce macroemulsion stability for a useful amount of time. Emulsions can be stabilized otherwise with polymers, solid particles or proteins.

Polyelectrolytes are charged polymers capable of stabilizing colloidal emulsions through electrostatic interactions. Their effectiveness can be dependent on molecular weight, pH, solvent polarity, ionic strength, and the hydrophilic-lipophilic balance (HLB). Stabilized emulsions are useful in many industrial processes, including deflocculation, drug delivery, petroleum waste treatment, and food technology.

A nanocapsule is a nanoscale shell made from a nontoxic polymer. They are vesicular systems made of a polymeric membrane which encapsulates an inner liquid core at the nanoscale. Nanocapsules have many uses, including promising medical applications for drug delivery, food enhancement, nutraceuticals, and for self-healing materials. The benefits of encapsulation methods are for protection of these substances to protect in the adverse environment, for controlled release, and for precision targeting. Nanocapsules can potentially be used as MRI-guided nanorobots or nanobots, although challenges remain.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

Droplet-based microfluidics manipulate discrete volumes of fluids in immiscible phases with low Reynolds number and laminar flow regimes. Interest in droplet-based microfluidics systems has been growing substantially in past decades. Microdroplets offer the feasibility of handling miniature volumes of fluids conveniently, provide better mixing, encapsulation, sorting, sensing and are suitable for high throughput experiments. Two immiscible phases used for the droplet based systems are referred to as the continuous phase and dispersed phase.

<span class="mw-page-title-main">Topical cream formulation</span>

Topical cream formulation is an emulsion semisolid dosage form that is used for skin external application. Most of the topical cream formulations contain more than 20 per cent of water and volatiles and/or less than 50 per cent of hydrocarbons, waxes, or polyethylene glycols as the vehicle for external skin application. In a topical cream formulation, ingredients are dissolved or dispersed in either a water-in-oil (W/O) emulsion or an oil-in-water (O/W) emulsion. The topical cream formulation has a higher content of oily substance than gel, but a lower content of oily ingredient than ointment. Therefore, the viscosity of topical cream formulation lies between gel and ointment. The pharmacological effect of the topical cream formulation is confined to the skin surface or within the skin. Topical cream formulation penetrates through the skin by transcellular route, intercellular route, or trans-appendageal route. Topical cream formulation is used for a wide range of diseases and conditions, including atopic dermatitis (eczema), psoriasis, skin infection, acne, and wart. Excipients found in a topical cream formulation include thickeners, emulsifying agents, preservatives, antioxidants, and buffer agents. Steps required to manufacture a topical cream formulation include excipient dissolution, phase mixing, introduction of active substances, and homogenization of the product mixture.

Chitosan-poly is a composite that has been increasingly used to create chitosan-poly(acrylic acid) nanoparticles. More recently, various composite forms have come out with poly(acrylic acid) being synthesized with chitosan which is often used in a variety of drug delivery processes. Chitosan which already features strong biodegradability and biocompatibility nature can be merged with polyacrylic acid to create hybrid nanoparticles that allow for greater adhesion qualities as well as promote the biocompatibility and homeostasis nature of chitosan poly(acrylic acid) complex. The synthesis of this material is essential in various applications and can allow for the creation of nanoparticles to facilitate a variety of dispersal and release behaviors and its ability to encapsulate a multitude of various drugs and particles.

<span class="mw-page-title-main">Polystyrene (drug delivery)</span> Polystyrene in drug delivery

Polystyrene is a synthetic hydrocarbon polymer that is widely adaptive and can be used for a variety of purposes in drug delivery. These methods include polystyrene microspheres, nanoparticles, and solid foams. In the biomedical engineering field, these methods assist researchers in drug delivery, diagnostics, and imaging strategies.

References

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