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9
Liquid andPolydisperse Systems:
Emulsions
K.Shubham, B.Behera, andMeenakshiK.Chauhan
Abstract
Many cosmetic, food, and pharmaceutical applications rely on emulsions.
Emulsions are thermodynamically unstable systems containing two immiscible
liquid phases. In emulsion, one phase is dispersed as globules in another phase.
Creams, ointments, gels, and pastes are emulsions that are commonly used for
the delivery of drugs. Simple water-in-oil (W/O) emulsions contain hydrophilic
drugs, while hydrophobic drugs are encapsulated within the oil droplets of oil-in-
water (O/W) emulsions. The primary objective is to protect the drug and bioac-
tive substances, thus increasing the bioavailability. Emulsions intended for oral
use can mask the drug’s bitter taste, while the topical delivery increases the per-
meability of bioactive agents. For pharmaceutical applications including taste
masking and vaccine adjuvants, multiple emulsions or double emulsions such as
water-in-oil-in-water (W/O/W) and oil-in-water-in-oil (O/W/O) are attractive
systems. These emulsions have smaller droplets in the dispersed phase that are
composed of the same components as the external phase. The variations in drop-
let size of the dispersed phase leads to the formation of microemulsion and nano-
emulsions. Microemulsions are a dispersion of oil, water, and an amphiphile.
They are optically isotropic and thermodynamically stable dispersions of either
W/O or O/W types. Microemulsions act as multifunctional carriers in addition to
tailoring nanoparticles. Miniemulsions, nanoemulsions, ultrane emulsions, and
submicron emulsions are dened as emulsions with droplet sizes between 20 and
200nm. These emulsions are clear because of the small droplets of the dispersed
phase, unlike coarse emulsions that appear milky. Emulsication refers to the
process of formation of emulsions. The aim of emulsication is to make a stable
system of two immiscible phases. The droplet size in a conventional emulsion
K. Shubham · B. Behera (*) · M. K. Chauhan (*)
Delhi Institute of Pharmaceutical Sciences and Research, DPSRU, New Delhi, Delhi, India
e-mail: beauty.behera@dpsru.edu.in; mkchauhan@dpsru.edu.in
220
grows with time leading to a separation of phases. Therefore, a third substance
such as stabilizers or emulsiers is added during the emulsication for long-term
stability. Emulsiers, which include phospholipids, polysaccharides, proteins,
small molecule surfactants, and other surface-active polymers, are often amphi-
philic compounds with both hydrophobic and hydrophilic groups on the same
molecule. The stability of an emulsion is dened by the capability of the phases
to remain mixed together and maintain their properties. The stability of such
systems is dependent on the dispersed phase’s droplet size, droplet size distribu-
tion, and differences in density, volume, and viscosities of the dispersed as well
as continuous phase. An emulsion may lose its stability through coalescence,
creaming, cracking, phase inversion, occulation, and Ostwald ripening. Several
theories have been proposed for the formation of stable emulsions considering
the various factors and emulsifying agents used. These theories explain the
behavior and action of the emulsiers at the interface of two immiscible liquids.
Some of these theories may be applicable to specic emulsifying agents under
some specic circumstances such as pH and proportion of both continuous and
dispersed phases. Molecular adsorption of small and large molecules to the drop-
let surface reduces the aggregation of the dispersed phase. The emulsion stability
is thus improved by the formation of a protective lm around the drop. This
chapter discusses recent advances in emulsion types, theories of emulsication,
formulations, and stability aspects of these biphasic systems.
Keywords
Emulsion · Flocculation · Ostwald ripening · Rheology · Spectrometry
9.1 Introduction
Many technological processes are based on the formation of a polydisperse group of
particles interacting with their surroundings. A collection of particles with varying
sizes that can evolve and form in a metastable environment make up this group. For
instance, such events and processes include the nucleation and development of crys-
tals in the metastable gas or liquid phase (Alexandrov etal. 2022). Dispersion refers
to systems that include at least two immiscible phases. A disperse system consists
of a dispersed phase in a dispersion medium also known as continuous phase
(Goodarzi and Zendehboudi 2019). The term “dispersions” includes generation of
reversible agglomerates containing two or more substances by hydrogen bond, van
der Waals forces, hydrophobic interaction, and physical attachments instead of
covalent bonds (Zhang etal. 2018). According to the state and type of the dispersed
phase, there are three basic types of dispersions (Fig.9.1) such as coarse disper-
sions, molecular dispersions, and colloidal dispersions (Zhang et al. 2018).
Emulsions are included in colloidal dispersions which consist of two immiscible
liquids stabilized by surfactant or emulsifying agents (Nikmaram etal. 2017). The
size of dispersed phase in an emulsion generally varies from 0.5 to 100 μm.
Emulsions are typically developed by a variety of chemical processes and use
K. Shubham et al.
221
small- and large-scale equipment, including homogenizers, ultrasonic processor,
magnetic stirrer, and rotor-stator mixer (Goodarzi and Zendehboudi 2019; Chen
etal. 2020a).
Majority of emulsions used in real-world applications are complex. The
International Union of Pure and Applied Chemistry (IUPAC) has developed the
denition of an emulsion. The IUPAC system states that in an emulsion liquid drop-
let and/or liquid crystals are dispersed in a “liquid” (Friberg etal. 1996). The unfa-
vourable interaction between the oil and water phases makes emulsion an unstable
system. In the absence of emulsiers, the emulsions begin to split/crack in distinct
layers due to differences in densities of the medium (Nour 2018). It is thus neces-
sary that stabilizers such as emulsiers are added to these formulations in order to
increase their long-term stability. Emulsiers, which include small molecule surfac-
tants, phospholipids, proteins, polysaccharides, and other surface-active polymers,
are generally amphiphilic compounds that include both hydrophilic and hydropho-
bic groups on the same molecule (McClements and Jafari 2018).
9.2 Classification ofEmulsions
The colloidal dispersions, also known as colloids, are combinations in which one
substance is very nely mixed with another. They have particle size between 1 and
100nm which is smaller than the particles present in a suspension. The emulsions
are colloidal dispersions which consist of two immiscible liquids stabilized by third
agent (Nikmaram etal. 2017). Commonly used examples of emulsions are milk,
cream, desserts, sauces, and mayonnaise. Based on the uid that becomes a continu-
ous phase, emulsions are categorized as water-in-oil (W/O) and oil-in-water (O/W).
The O/W emulsions are produced when oil is dispersed in the water or aqueous
phase. These emulsions are commonly used to protect, encapsulate, or control the
release of bioactive agents (Lu etal. 2021). Emulsions of W/O are formed when
water or aqueous phase of droplets is dispersed in the oil phase. In W/O emulsions,
the arrangement of emulsier molecules is opposite to that observed in O/W type.
The non-polar tails are pointed towards the oil phase and polar heads are oriented
towards the water droplets. The use of emulsiers depends on the type of emulsions
Fig. 9.1 Classication of dispersions based on the size of dispersed phase
9 Liquid andPolydisperse Systems: Emulsions
222
to be prepared (Table9.1). Emulsions can be also classied on the basis of the size
of dispersed phase into macroemulsions, microemulsions, nanoemulsions, and
pickering emulsions (Aslam et al. 2023; Juneja et al. 2022; Lipei etal. 2021; Suthar
et al. 2023). The following section discusses in brief the various emulsion systems.
9.2.1 Macroemulsion
Macroemulsions are classied as W/O, O/W, and multiple or complex or double
emulsions. If the dispersed droplets in the emulsion are between 0.1 and 100μm, it
is referred to as a macroemulsion (Nikmaram etal. 2017). This group includes most
of the emulsions that are manufactured in the market. Macroemulsions with diam-
eters more than 100μm are thermodynamically unstable and rarely maintain their
initial drop state (Kim etal. 2022). Generally, a phase is labelled as the dispersed
phase if its volume percentage is lower than that of the other phase, which is labelled
as the continuous phase. In W/O type macroemulsion, oil is the continuous oil
phase. When it comes to oil-based emulsions, the most widely manufactured emul-
sions fall under the W/O category. A number of variables, including temperature
and the W/O ratio, affect these types of emulsions. Sometimes, the reverse emul-
sions are also known as O/W emulsions (Glatter and Salentinig 2020). Reverse
emulsions are used as a vehicle for parenteral drug administration as well as in food
and cosmetic industries (Prankerd and Stella 1990).
The complex and heterogeneous dispersion systems known as multiple or double
emulsions are made of small droplets in bigger droplets and are suspended in a
continuous phase. Oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W)
multiple emulsions are the two main forms of these systems. In an O/W/O emul-
sion, the oil droplets are suspended in bigger water droplets that are suspended in a
Table 9.1 Classication of emulsions
Emulsions
Types Emulsifying agent
Size range
Macroemulsion O/W Gelatin, tween 80 (polyoxyethylene sorbitan
monooleate)
0.1–5μm
W/O Beeswax, span 80 (sorbitan monooleate)
0.1–5μm
Multiple/double
emulsion
O/W/O Polyoxyethylene di-isostearate,
polyoxyethylene di-oleate, microcrystalline
wax
0.1–100μm
W/O/W Guar gum, sodium caseinate, maltodextrin
0.1–100μm
Microemulsion W/O Span 20 and/or absolute butanol as
co-surfactant
1–100nm
O/W Tween 20/80 (polysorbate 20) and/or
Cremophor EL (polyoxyl 35 castor oil)
1–100nm
Nanoemulsion O/W
β-Lactoglobulin
10–500nm
W/O Span 80 (sorbitan monooleate) 10–500nm
Pickering emulsion O/W Sodium stearoyl lactylate 0.1–4200nm
W/O Whey protein-polyphenol complex particles
0.1–5μm
K. Shubham et al.
223
continuous oil phase. Similarly, W/O/W is made of water droplets suspended in
bigger oil droplets which is further emulsied in a continuous aqueous phase. Both
the O/W/O and W/O/W multiple emulsion systems have been used for drug delivery
applications by the pharmaceutical industries (Jena etal. 2018). These multiple sys-
tems require two or more emulsiers during their formation. One of the emulsiers
stabilizes the W/O emulsion primarily through hydrophobic interactions, whereas
the other stabilizes the O/W emulsion primarily through hydrophilic interactions. In
addition to interfering with each other’s ability to stabilize, both surfactants may
interact with both surfaces. Furthermore, the composition of the binary surfactant
mixture controls the lifetime of the lms at the interfaces as well as their permeation
characteristics (Cunha etal. 2014).
9.2.2 Microemulsion
A different class of emulsions known as microemulsions exists, which is distinct
from macroemulsions. When two immiscible liquids come in contact, it results in
the formation of this type of emulsion, due to their low interfacial energy (Fig.9.2).
The stability and formulation aspects of microemulsions are often different from
those of macroemulsions (Goodarzi and Zendehboudi 2019; Pardhi et al. 2022).
Microemulsions are isotropic, transparent solutions and are thermodynamically
stable. It consists of at least a hydrophobic, a hydrophilic, and an amphiphilic com-
ponent. Their thermodynamic stability and signicantly lower structural size
Fig. 9.2 Ternary phase diagram for the formation of microemulsion
9 Liquid andPolydisperse Systems: Emulsions
224
(3–30nm) provide them a unique edge over conventional emulsions. These two
characteristics translate them into the long-term stabilization of mixed apolar/polar
systems that would be impossible to achieve in a conventional emulsion (Hejazifar
etal. 2020). Microemulsions are a exible carrier with a number of prominent char-
acteristics, including very low surface tension, effective absorption, improved bio-
availability of poorly soluble drugs, penetration due to its small droplet size, and
inexpensive approach of formulation. Typically, the formulation of a microemulsion
is characterized by using the ternary phase diagram. This ternary phase diagram is
represented by a triangle with concentration of oil, water, and surfactants at three
sides. Co-surfactants are considered as pseudo-components and used in microemul-
sions at a predetermined ratio with surfactants (Shukla etal. 2018). Apart from
pharmaceutical and nutraceutical, microemulsion is one of the most signicant
chemical ooding agents and an effective tool for oil recovery because of its high
degree of oil extraction efciency (Pal etal. 2019).
9.2.3 Nanoemulsion
Nanoemulsions are also categorized into O/W and W/O dispersion systems of two
immiscible liquids stabilized using a suitable emulsier. The mean droplet diameter
of dispersed phase in a nanoemulsion is usually less than 500nm. Compared to the
milky white colour of a coarse emulsion (whose tiny droplets participate in multiple
light scattering processes), their appearance is clear or hazy due to the small droplet
size. Miniemulsion or submicron emulsion is occasionally used interchangeably
with the term nanoemulsion; however, it should not be confounded with microemul-
sion. Although nanoemulsions and microemulsions have the same range of droplet
size, they differ greatly in terms of structural features and prolonged thermody-
namic stability (Kumar et al. 2021; Singh et al. 2017; Sudhar et al. 2022).
Nanoemulsions have higher kinetic stability than coarse emulsions. They possess a
large solubilization capacity than simple micellar dispersions. They have been used
in the pesticide and cosmetic industries as an aqueous base for organic deliveries.
The small droplet size of nanoemulsions directly affects their long-term physical
stability by hindering traditional destabilization processes such as coalescence,
creaming, and sedimentation (Singh etal. 2017). Nanoemulsions are used to deliver
a variety of drugs through oral, ocular, parenteral, topical, and transdermal route
(Vv etal. 2018).
9.2.4 Pickering Emulsion
Pickering emulsions have solid particles at the oil-water interface. Unlike tradi-
tional emulsions that use surfactants, solid particles are adsorbed at the interface in
a pickering emulsions. The solid particles such as clay, protein particles, or colloidal
silica irreversibly adsorb to the interface and form a barrier that prevents the drop-
lets from aggregating or coalescing. The three-phase contact angle of the particles
with the interface determines their wettability, which in turn inuences the type of
K. Shubham et al.
225
pickering emulsion that forms such as W/O or O/W.The W/O emulsions are stabi-
lized by hydrophobic particles (contact angle is greater than 90°), whereas O/W
emulsions are stabilized by more hydrophilic particles (contact angle is less than
90°). The benets of these systems are that they offer greater stability against
coalescence and good biocompatibility when employing food-grade particles and
have the capacity to introduce new functionality to the emulsion. They are used in a
number of elds, including cosmetics, medicines, food, and increased oil recovery
(Yang etal. 2017).
9.3 Theories ofEmulsions
The formulation and stability of the emulsions depend critically on the adsorption
of nanoparticles, proteins, polymers, or surfactants to the interface. During the
emulsication process, a greater interfacial area is created more favourably by the
surfactant adsorption, which reduces the interfacial tension and, consequently, the
surface free energy of the liquid-liquid system (Llamas etal. 2018). There are vari-
ous indispensable factors that result in the production of a stable emulsion.
Numerous theories have been postulated earlier to explain the stabilization behav-
iour of an emulsion. The following section discusses these theories.
9.3.1 Fischer’s Theory ofHydrates andSolvates
Fischer’s hydration theory states that the emulsifying agents are used in particular
proportion to continuous phase, resulting in the formation of colloidal hydrate. The
other phase is dispersed in the colloidal hydrate. This theory is unable to explain
certain observable facts and contradicts others. Therefore, it cannot be considered
an acceptable emulsion theory (Roberts 2002).
9.3.2 Surface Tension Theory
After much research, it was found that the surface tension theory, or, more accu-
rately, the interfacial tension theory, was sufcient to explain the development and
stability of numerous emulsions. This theory states that the emulsifying agents
reduce the interfacial tension between the two immiscible liquids, which reduce the
repelling force between them and eliminate the attraction that the liquids have for
their own molecules. Interfacial tension is the force that prevents two immiscible
liquids from breaking when they come into contact. When two liquids have a high
interfacial tension, emulsication is challenging; nevertheless, emulsication is
made easier when the tension is decreased. The theory states that with the dispersion
of oil in water, the interfacial tension is so high that as two globules of the dispersed
phase approach one another, the liquid is drawn out from between them, causing
them to coalesce. The globules remain separated when the addition of an emulsier
9 Liquid andPolydisperse Systems: Emulsions
226
signicantly lowers the interfacial tension. This hypothesis has been incorporated
into the more recent and generally recognized adsorption lm theory, which explains
emulsion development and stability on the creation of an adsorbed lm at the inter-
face. According to the plastic or interfacial lm theory, the emulsifying agent sur-
rounds the internal phase droplets as a thin layer of lm adsorbed on their surface,
located at the interface between the oil and water. This lm keeps the dispersed
phase from coming into contact and merging. The formulation of a W/O or O/W
emulsion is dependent on the degree of solubility of the agent in the two phases. The
water-soluble emulsiers promote O/W emulsions, while oil-soluble emulsiers
promote W/O emulsions (Roberts 2002).
9.3.3 Molecular Adsorption Theory
Amphiphiles, or surface-acting agents, form a monomolecular lm by their adsorp-
tion at the oil-water interface which lowers the interfacial tension between two liq-
uids. As per the theory, surfactants are examples of emulsifying agents that have
both non-polar (hydrophobic) and polar (hydrophilic) components in their mole-
cules. When these are added to an oil-water system, the molecules of surfactant
align themselves at the interface, with their non-polar portions in the oil phase and
their polar portions in the water phase. This orientation lowers the interfacial ten-
sion between the two liquids by producing a monomolecular layer of surfactant
molecules at the interface. The decrease in the interfacial tension during homogeni-
sation causes large droplets to break into smaller ones, forming a stable emulsion.
Nowadays, emulsions are usually prepared using a blend of emulsiers rather than
a single agent. A complicated lm forms at the interface between a hydrophobic
agent in the oil phase and a hydrophilic emulsier in the aqueous phase. Surfactant
adsorption at the liquid interfaces thus inuences the stability of emulsions by
reducing interfacial tension, enhancing electric double-layer repulsion (ionic sur-
factants), and improving surface elasticity. Additionally, the nature of the surfactant
can regulate how the phases in an emulsion are arranged, i.e. which phase will form
the continuous phase and which will form the dispersed phase (Umar etal. 2018).
9.3.4 Oriented Wedge Theory
This theory describes how an emulsifying agent’s curved monomolecular layer
forms around a droplet of the emulsion’s internal phase (Pratishtha etal. 2021).
Emulsifying agents align themselves based on solubility since they contain both
hydrophilic and hydrophobic portions. Emulsifying agents having a higher propor-
tion of hydrophobic portions than hydrophilic ones promote the W/O emulsion and
vice versa. Surfactants, which have a small group within and a bulky group outside,
are always found on the surface of a droplet, such as a wedge, due to packing restric-
tions at the water/oil interface of emulsion drops (Wang etal. 2023).
K. Shubham et al.
227
9.4 Formulation
The emulsication process involves the breakdown of one liquid phase within the
other, resulting in the production of an immense number of tiny droplets. Emulsions
can be produced in research or industrial elds, using high or low energy proce-
dures. They are prepared on a large scale using micro-uidizers, shear mixers, soni-
cators, and high-pressure valve or membrane homogenizers. The technique selected
relies on the emulsier type and the eld of application (Ravera et al. 2021).
Emulsication involves two competing processes that occur at the same time. The
rst process involves the breaking of the dispersed phase into droplets, while the
second is coalescence of the produced droplets. This can cause a condition in mix-
ing devices called “morphological hysteresis”. The emulsiers serve the purpose of
preventing the droplets from merging with one another, which is necessary to guar-
antee that the droplet size distribution stays steady. The interfacial tension between
the dispersed and continuous phases is lowered in the presence of appropriate emul-
siers, which lowers the energy needed to build a new interface and promotes the
production of droplets. Furthermore, as previously indicated, the emulsiers can
give the nal emulsied products an appropriate lifetime and an energy barrier
against coalescence (Ho etal. 2024).
9.4.1 Method ofPreparation
9.4.1.1 Dry Gum Method
Dry gum method is also known as gum acacia method. This method includes four
parts of oil, two parts of water, and one part of gum as an emulsifying agent. The
gum is initially mixed with the right amount of oil so that the powder is thoroughly
wetted. The mixture is then vigorously triturated with water until the emulsion
becomes creamy white and has a “crackling” sound. The preservatives, colorant,
and avouring agents can be added to improve the palatability (Kale and Deore 2017).
9.4.1.2 Wet Gum Method
This method uses a 4:2:1 ratio of oil, water, and emulsier, respectively. However,
the sequence of mixing is different. The gum is rst triturated with water to form
mucilage. The oil is then slowly added while triturating. Then, the mixture is tritu-
rated for few minutes to formulate the emulsion. This method is more difcult to
execute well, particularly with more viscous oils, but it may yield a more stable
emulsion (Kale and Deore 2017).
9.4.1.3 Bottle Method
This approach can be used to create emulsions of volatile oils and oleaginous com-
pounds having very low viscosities. This method is a modication of the dry gum
method. In this method, gum is added to a dry bottle, followed by oil. The bottle is
9 Liquid andPolydisperse Systems: Emulsions
228
capped and shaken vigorously. Desired volume of water is then added all at once,
and the mixture is vigorously agitated to form emulsion (Gowda etal. 2013).
9.4.1.4 In Situ Soap Method
Emulsions can be prepared using in situ soap method, in which soap molecules are
formed while the emulsion is being prepared. In this method the aqueous phase
contains water and an alkaline material like potassium or sodium hydroxide. The
alkaline material creates soap molecules in situ by reacting with the fatty acids in
the oil phase. These soap molecules act as emulsiers and stabilize the resulting
emulsion (Saygı-Arslan etal. 2009).
9.4.1.5 Phase Titration Method
The required quantity of medication is dispersed in the accurate amount of oil to
create a microemulsion, which is necessary for the drug to become soluble. The
mixture is then thoroughly mixed and the appropriate amount of surfactant added,
along with a small amount of co-surfactant blend which is added with stirring.
Drop-by-drop double-distilled water is added while stirring around 10min to form
emulsion. The stirring rate can be adjusted to meet the requirements of the particle
size (Kale and Deore 2017).
9.4.1.6 Phase Inversion Temperature Method
Phase inversion temperature (PIT) method is a low-energy emulsication technique
that modies temperature to alter the optimal curvature of surfactants at constant
composition to form nanoemulsions. Nanoemulsions are formed by the preparation
of microemulsions at its PIT followed by quickly cooling them to room tempera-
ture. This can be divided into three main steps. First, the oil, water, and non-ionic
surfactant are stirred at room temperature to produce a coarse emulsion. Second, the
mixture is slowly heated to a temperature near or above the PIT.Lastly, the solution
is rapidly cooled to room temperature while continuously stirred, resulting in the
creation of nanoemulsions (Jintapattanakit 2018).
9.4.1.7 Spontaneous Emulsification
The transfer of water-miscible components (surfactant, co-surfactant, and solvent)
from an organic phase into the aqueous phase is caused by diffusion, which occurs
when the system is diluted. In spontaneous emulsication, the aqueous phases that
contain water and co-surfactant are typically combined with an organic phase that
contains oil and hydrophilic surfactant. The rapid migration of water-miscible com-
ponents into the aqueous phase generates enormous turbulence at the interface of
the two phases, resulting in a signicant increase in the oil-water interface area. It
causes the spontaneous production of oil droplets surrounded by an aqueous phase
via the budding process (Jintapattanakit 2018).
K. Shubham et al.