A Review on Multiple Emulsion

Sayyed Ahamad  Sayyed Kaleem *, Dr. G.J. Khan, Amliwala Hamza Ilyas, Mansoori Safwan Salim ,Shah Afrin Salim.

J.I.I.U’S Ali-Allana College of Pharmacy Akkalkuwa, Dist.- Nandurbar (425415) Maharashtra, India.

Abstract: Emulsions are complex colloidal systems widely employed in various industries, owing to their ability to mix immiscible liquids, such as oil and water, through the use of emulsifying agents. This review article provides a comprehensive overview of emulsions, encompassing their types, advantages, disadvantages, multiple emulsions, preparation methods, stabilization mechanisms, double emulsification techniques, applications, and a conclusion highlighting their significance. The exploration begins with an introduction to emulsions as crucial components in sectors ranging from food to pharmaceuticals. The primary focus is on the three primary emulsion types: oil-in-water (O/W), water-in-oil (W/O), and the intricate multiple emulsions (W/O/W or O/W/O). The advantages and disadvantages of emulsions are examined, emphasizing their role in enhancing stability, solubility, and controlled release while addressing issues of phase separation and shelf life. Additionally, the double technique of emulsification is presented as a key method for crafting multiple emulsions These applications encompass flavor delivery, drug formulation, skincare products, and more. In conclusion, this review serves as a valuable resource for understanding emulsions and their manifold utility in modern industrial processes Keywords: Emulsions, Colloidal systems, Oil-in-water (O/W),Water-in-oil (W/O), Multiple emulsions

Corresponding Author: Sayyed Ahamad  Sayyed Kaleem Email ID: aksayyed13@gmail.com

Article History Received:        25/09/2023 Accepted:        25/10/2023 Published:       06/11/2023

 

 

 

 

 

 

 

 

 

 

 

 

 

 INTRODUCTION:

Some foods are even created with some degree of emulsion, and many naturally occurring and processed meals contain emulsions in some form or another. In general, a "emulsion" is a structure that results from the dispersion of one immiscible liquid into the other in the form of minute droplets. Definition and explanation of terms like "macro emulsion," "Nano emulsion," and "multiple emulsions" are essential to comprehending the numerous emulsion types. Nano emulsions are becoming more significant in the food industry as a cutting-edge means of delivering functional ingredients. The application potential of multiple emulsions (W/O/W) in the food industry is also said to be rather high. Numerous emulsions are used in culinary applications to achieve two crucial strategic goals contain a variety of fragrances, therapeutic compounds, or delicate culinary additives. This essay provides a thorough explanation of the various types of emulsions, the role of various emulsifying agents, and potential uses for emulsions in the food industry.

Various emulsion types

The three primary types of emulsions are water-in-oil-in-water (W/O/W), complex emulsions like oil-in-water (O/W), and oil-in-water (O/W). The difficult emulsion is also known as a multiple emulsion [5]. The three forms of emulsion are displayed in

A water-in-oil emulsion is a type of emulsion in which the continuous phase is frequently made up of hydrophobic materials, like oil, and the dispersed phase is water [7].

More than 95% of the crude oil emulsion that develops in the oil field is of the W/O type [8]. The W/O emulsions, as shown in the example in, consist of three elements: water, a surfactant, and a solvent. A water-in-oil emulsion is a form of emulsion in which the dispersed phase is typically made up of water and the continuous phase is frequently made up of hydrophobic materials, such as oil [7].

The W/O type makes up more than 95% of the crude oil emulsion that forms in the oil field [8]. Water, a surfactant, and a solvent are the three components that make up W/O emulsions, as demonstrated in the example. According to the study, there are four possible states of water and oxygen mixtures: stable, mesostable, unstable, and entrained water. Stable emulsions are brown in color and contain 60 to 80 percent water. Examples of meso stable emulsions are O/W emulsions are frequently brown or black and fall somewhere between stable and unstable emulsions in terms of their properties.

Emulsions that swiftly split into two phases of oil and water are said to be unstable emulsions.In the end, the entrained water is black in color and has a water content of 30 to 40%. Over the course of a week, it will eventually remain at 10%. Only the stable and mesostable states are considered to be separate from the other two states and to qualify as emulsions.

 

 

 

 

 

OIL AND WATER

Are frequently brown or black and fall somewhere between stable and unstable emulsions in terms of their properties. Emulsions that swiftly split into two phases of oil and water are said to be unstable emulsions. In the end, the entrained water is black in color and has a water content of 30 to 40%. Over the course of a week, it will eventually remain at 10%. Only the stable and mesostable states are considered to be separate from the other two states and to qualify as emulsions.

Figure  Surfactant films at the water–oil interface in o/w and w/o emulsions:

 (a) formation of a monomolecular film at the oil–water interface for the stabilisation of o/w emulsions;

(b) stabilisation of w/o emulsions by the oriented adsorption of divalent soap salts

 

Multiple emulsions

Different emulsions, such as water-in-oil-in-water (W/O/W) and oil-in-water-in-oil (O/W/O), may be encountered. Multiple emulsions are often stabilized by combining hydrophilic and hydrophobic surfactants. The more complex multiple emulsions consist of very small droplets suspended in bigger droplets that are also dispersed in a continuous phase.

As observed in Fig. 1, the W/O/W emulsions, for example, are composed of increasingly suspended water droplets that are caught in larger oil droplets. Additionally, these emulsions call for the addition of at least two emulsifiers to the system.

Systems with numerous emulsions are complicated. They have been shown to be safe in the realms of separation, cosmetic pharmaceuticals, and pharmacy and can be thought of as emulsions of emulsions. In this advanced type of emulsion system, the oil-in-water or water-in-oil emulsions are dispersed in another liquid medium. Thus, a water-in-oil-in-water (W/O/W) emulsion is composed of water droplets dispersed in the oil phase of an oil-in-water emulsion, whereas an oil-in-water-in-oil (O/W/O) emulsion is composed of incredibly small oil droplets spread in the water globules of a water-in-oil emulsion..

Taste masking, adjuvant vaccines, immobilization of enzymes and sorbent reservoir of overdose therapies, and occasionally for the enhancement of dermal or exterior skin absorption are some of their medicinal applications. Many emulsions, including skin moisturizers, have been created as cosmetics. Multiple emulsions can also be used to provide prolonged release. These systems have some benefits, such as the ability to incorporate multiple active ingredients in various compartments and the protection of the captured molecules. Despite their significance, multiple emulsions are constrained by their complicated structure and thermodynamic instability.

Advantages and Disadvantages of emulsions as Dosage forms

ADVANTAGES

v  Oils that are unpleasant to swallow can be provided in a pleasant form.The aqueous phase is easily flavored.

v  The taste of oils can be masked.

v  Absorption is faster when compared to solid dosage forms.

v  It is possible to include two incompatible ingredients, one in each phase of the emulsion.

v  Emulsions of the O/W type are administered orally for the following purposes:

v  Disguise the taste or oiliness of medicinal oils such as liquid paraffin and cod liver oil. The aqueous continuous phase, which will be pleasantly flavored, isolates the unpleasant disperse phase from the tongue and, if the patient wishes, allows the residue of the dose to be rinsed easily from the mouth with water.

v  To improve the absorption of oils

v  Sometimes O/W emulsions of nutritive oils and fats are administered intravenously to patients who are unable to ingest food in the normal way.

v  Semisolid emulsions are O/W (vanishing creams) or W/O (cold creams). O/W emulsions are preferred over W/O emulsions. They can be easily rubbed into the skin and can be easily removed by washing

 

DISADVANTAGES

v  Calculation of primary emulsion formulae and technical expertise are needed for the manufacture of stable emulsions.

v  A measuring device is needed for administration.

v  Emulsions require shaking before use to ensure uniformity of dose.

v  If the preparation is not shaken well, the accuracy of the dose is likely to be less when compared to solutions.

v  Improper storage conditions can affect the disperse system.

v  Since emulsions are stored in glass or plastic containers, they are bulky, difficult to transport, and prone to container breakages.

v  Microbial contamination of emulsions can lead to cracking.

 

MULTIPLE EMULSIONS

             Multiple emulsions are intricate polydisperse systems in which emulsions of oil in water and water in oil coexist and are stabilized by hydrophilic and lipophilic surfactants, respectively. In order to create stable multiple emulsions, the ratio of these surfactants is crucial. There are two types of multiple emulsions: water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o). For numerous emulsions, formulation, preparation procedures, and in vitro characterization techniques are reviewed. With particular reference to w/o/w type multiple emulsions, many aspects impacting the stabilization of multiple emulsions and stabilization techniques are covered in detail. They are an adaptable carrier due to the favorable drug release mechanisms and/or rates and in vivo fate of various emulsions. It has a wide range of uses, including targeted delivery, bioavailability augmentation, enzyme immobilization, taste masking, and controlled or sustained drug delivery. In order to deliver hydrophilic pharmaceuticals orally, which are unstable in the gastrointestinal tract like proteins and peptides, multiple emulsions have also been used as an intermediary stage in the microencapsulation process.

       The development of methods for the manufacture, stabilization, and rheological analysis of numerous emulsions will enable the development of innovative carrier systems for pharmaceutical, cosmetic, and therapeutic substances. The focus of this review is on multiple emulsion system composition, stabilizing methods, and prospective applications.

TYPES

Oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) multiple emulsions are subcategories of Types A, B, or C multiple emulsions. Oil makes up both the internal droplets and the external continuous phase (matrix) of an O/W/O multiple emulsion. The interior oil droplets are separated from the exterior oil phase by the aqueous phase. In the continuous aqueous phase, the water-in-oil (W/O) emulsion itself is dispersed as enormous droplets. The components of a W/O/W multiple emulsion are tiny water droplets dispersed in oil.

 

 

Water, oil, and water

An organic phase that is hydrophobic separates the internal and external aqueous phases of the W/O/W system. In other words, the W/O/W system is one in which one or more water droplets are enclosed within an aqueous phase that surrounds one or more oil droplets. The "liquid membrane" is an immiscible oil phase that separates two miscible water phases and functions as a diffusion barrier and semipermeable membrane for the pharmaceuticals or moieties trapped in the interior aqueous phase.

Each inner aqueous droplet is separated from the outside aqueous phase by an oil phase layer, which is made up of dispersed oil globules that also contain smaller aqueous droplets. There must be at least two surfactants in the mixture.

Preparation of W/O/W emulsions:-

        W/O/W emulsions were made using a two-step emulsification process. The internal and exterior water phases were both composed of 9 Milli-Q water. The oil phases contained the lipophilic emulsifiers. The preparation process is streamlined in Fig. 1. 1 To form primary water-in-oil (W/O) emulsions, the internal water phase, lipophilic emulsifier, and oil phase were combined. The mixture was then agitated at 25000 rpm for three minutes using an Ultra-Turrax dispersion device (T10, IKA, Germany). ATS Engineering in the US produced a Nano homogenizer, which was used to homogenize the mixture for 4 passes. To form two W/O/W emulsions, the previous W/O emulsions (20 wt%) were mixed with the external water phase (80 wt%), which was then homogenized three times over the course of two minutes at 10,000 rpm. To do this, the oil-water contact was stabilized using a hydrophilic emulsifier.

Fig. The preparation process of the W/O/W emulsions

 

W/O/W emulsions with different lipophilic and hydrophilic emulsifiers.

       The hydrophilic emulsifier (Tween 80) was fixed at 5 weight percent for the single factor experiment with the lipophilic emulsifier, and the ratios of the oil phase to the internal water phase (O[thin space (1/6-em)]:[thin space (1/6-em)]) were adjusted.W2 [thin at 80[thin space (1/6- em)]:[thin space (1/6- em)] and the external water phase to the W/O emulsion phase 20 (w/w); different lipophilic emulsifiers (PGPR, Span 80, GMS, and lecithin) made up 5% of the oil phase. The lipophilic emulsifier (PGPR, 5 wt%) was fixed, the other parameters were maintained, and a different type of hydrophilic emulsifier was used to form W/O/W emulsions in the single factor experiment.

Oil, water, and oil:-

Internal and external oil phases are separated in the O/W/O system by an aqueous phase (hydrophilic). In other words, the O/W/O system allows for the possibility of water droplets around one or more oil droplets in the oil phase.

There is a water phase, an outside oil phase, and an inner oil phase. The inner oil phase is first mixed with the water to form an oil-in-water emulsion. The subsequent distribution of the o/w emulsion in the outer oil phases results in the o/w/o type multiple emulsion.

PREPRATION

 There are typically two phases involved in creating numerous emulsions. In the initial stage, the main emulsion is created. When creating a W/O/W multiple emulsion, the primary emulsion is a simple W/O (water droplets-in-matrix oil) emulsion using a low HLB (hydrophilic-lipophilic balance) surfactant in a water and oil solution. Oil and a water solution with a high HLB surfactant concentration are used to make a simple O/W (oil droplets in matrix water) emulsion as the main component of an O/W/O multiple emulsion. The second phase involves re-emulsifying the primary emulsion (W/O or O/W), either in an oil solution with a low HLB surfactant to produce an O/W/O two emulsion.

       The second emulsification step is carried out in a low shear apparatus in order to prevent the expulsion of interior droplets into the external continuous phase.

       A primary emulsion can be re-emulsified to create many emulsions, or an emulsion can invert from one type to another, such as from W/O to O/W, to create multiple emulsions. Because the internal dispersed phase of O/W emulsions is minimal, they are not employed in therapeutics.

Mechanisms of emulsion stabilization:-

Emulsions are employed in a wide range of industries, including the production and refinement of petroleum as well as the food and pharmaceutical industries. The stability of the emulsion is influenced by the interfacial barrier, which stops the scattered water droplets from coalescing. The stability of the emulsion is influenced by the interface film and the general surfactant adsorption process. Emulsion stabilization can be accomplished in four different ways. The Maranon-Gibbs effect, steric repulsion, thin film stabilization, and electrostatic repulsion are the next four phenomena [21]. The following subsections cover these four mechanisms.

Electrostatic repulsion:-

Electrostatic force, which tends to prevent droplet contact, is produced by the interaction of the electrical double layers surrounding the charged droplets. This process involves the adsorption of an ionic surfactant. Electrostatic repulsion does not greatly aid in the stability of water-in-oil emulsions due to the low dielectric constant of the continuous phase. Electrostatic forces do not contribute to the stability of the emulsion; rather, the interfacial film strength defending the scattered droplets does.

Fig..Schematic representation of electrostatic stabilization

Steric repulsion

In systems stabilized by non-ionic surfactants and polymers, steric stabilization is typically present. The surfactant molecules in this method will cover the scattered water droplets, and the surfactant tail deposited on the surface of the particles prevents droplets from coming into close contact, as seen in Since these kinds of stabilizers contain a polar part with a strong affinity to the aqueous phase or water and a non-polar part with a strong affinity to oil, they are primarily responsible for stabilizing W/O emulsions.

Double Technique of Emulsification

         According to Gregory and Miller (2009), double emulsions can either be of the W/O/W type (smaller aqueous droplets in dispersed oil globules) or the O/W/O type (smaller oily dispersed droplets in dispersed aqueous globules). Usually, two surfactants are used to form these emulsions in two phases. While the surface contact of the oil globules in W/O/W emulsions must be stabilized by a hydrophilic substance, the internal interface of the W/O emulsion must be stabilized by a hydrophobic component. The concepts of the emulsion-diffusion process and Nano precipitation are combined in a process known as double-emulsion production to produce Nano capsules. The W/O emulsion's oily phase is originally changed by an organic.

        Double-emulsion manufacturing, a method that combines the concepts of the emulsion-diffusion process and nanoprecipitation, is used to produce Nano capsules. The film-forming polymer, W/O surfactant, and a solvent that is totally or partially miscible in water replace the oily phase in the W/O emulsion before it. The aqueous phase containing a stabilizing agent is then added to form the water in organic in water emulsion. When nanostructure hardening is produced by polymer precipitation and solvent diffusion (Mora-Hearts et al., 2010). It has been shown that modifying the W/O emulsion, stabilizing agent type, and concentration all have an effect on the average Nano capsule size and the effectiveness of the active ingredient.

Applications:-

Multiple emulsions are especially helpful because of their vesicular structure, which possesses a selective permeability characteristic of liquid membranes and an interior phase very comparable to that of liposomal vesicles. An O/W/O multiple emulsion may seem more advantageous since the additional partitioning step with the medication initially in the internal oil phase is thought to be the rate-limiting component that may define the drug release characteristics. As a result of biological fluids' compatibility with water, oil, and water (W/O/W), multiple emulsions are frequently utilized in these applications.

It is intended to perform essentially as a straightforward W/O emulsion after parenteral injection [7]. Additionally, external water phase administration is much simpler than with excessively thick and difficult W/O emulsions (oil is an exterior phase).

Advantages of Multiple Emulsions

v  They can cover up the unpleasant flavors and odors of medications, making them more acceptable. For instance, chloroquine phosphate, cod liver oil, castor oil, and so on

v  These can be utilized to extend the drug's release, resulting in prolonged release activity.

v  Patients who are bedridden can receive sterile intravenous emulsions containing essential foods such as vitamins, lipids, and carbs.

v  Drugs that are vulnerable to oxidation or hydrolysis are protected by emulsions.

v  To aid in diagnosis, intravenous emulsions containing contrast media have been produced.

v  Emulsions are frequently used to create items that are applied externally, such as lotions, creams, and liniments; g. improvement of dermal or enteric absorption

Many emulsions' drawbacks

The main problem with multiple emulsions is that they have complicated structures and are thermodynamically unstable, which greatly limits their use in the different applications for multiple emulsions.

Disadvantages:-

v  Thermodynamically unstable, have complex structure, which leads to short shelf life of product

v  These are packaged in a plastic/glass co

 

CONCLUSION:

         The multiple emulsion is one of the most advanced drug delivery methods for improving the numerous characteristics of medicines, such as bioavailability, taste, release rate, etc. The enhancements comprise several distinctive formulations that can be integrated into other formulations to enhance the flavor and simplicity of administration of the medication. An emulsion is embedded in another emulsion in the complicated polydisperse system known as many emulsions. It can be used to distribute unstable medications, conceal flavors, give them a continuous release, stop them from leaking into the environment, among other things.

 

ACKNOWLEDGMENT

Authors are thankful to Principal and Management J.I.I.U' S Ali Allana College of Pharmacy Akkalkuwa, Dist. Nandurbar for providing moral support and necessary facilities for completion of this work.

 

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