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Emulsion Formulation

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Emulsion Formulation

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manel.k579
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Chapter III Emulsion Formulation

Emulsions, Microemulsions, and


Lipid-Based Drug Delivery Systems
for Drug Solubilization and Delivery.
Part: I Parenteral Applications.
INTRODUCTION

Over the past several decades, emulsion formulations have been explored for
resolving a variety of
drug delivery challenges. Unlike solutions for oral or parenteral administrations, which are
usually
homogeneous one-phase systems or molecular dispersions, emulsions are colloidal
dispersions of
at least two immiscible phases stabilized with the aid of a third component generally
referred to as
the emulsifying agent.

Most of the advantages of emulsion systems over conventional dosage forms


such as oral solutions and liquid injectables can be attributed to this stable heterogeneity,
and their
ability to deliver immiscible phases in a reliable and reproducible manner. This chapter
focuses on
demonstrating the usefulness of emulsion systems for the delivery of water-insoluble
compounds
for enteral and parenteral administration.

Definition

These are dispersed systems, a first liquid divided in the form of fine droplets in a
second liquid immiscible with the first.

An emulsion can be defined as a mixture of two immiscible phases (namely, water and
oil) with an emulsifier added to stabilize the dispersed droplets (Davis et al., 1987). As
conventionally defined, emulsions will have droplet diameters of more than 100 nm (up to 50
µm), and thus are opaque or milky in appearance.

In addition, they are thermodynamically unstable by nature, that is, on standing


they will eventually separate into two phases. However, proper choice of emulsifier (generally
1%–5%) and preparation conditions can delay this separation and thus lead to nominal shelf
lives of more than 2 years, as typically required for pharmaceutical products. An emulsion
can be characterized as oil-in-water (o/w) (containing up to 40% oil) or water-in-oil (w/o),
depending on the identity of the dispersed and continuous phases. Multiple (e.g., w/o/w)
emulsions can also be prepared, but these are less widely used in pharmaceutical applications.

Whereas microemulsions have found applications in oral use, parenteral use of


microemulsions has been less common owing to toxicity concerns (e.g., hemolysis) arising
from the high surfactant and cosolvent levels.
Typically, emulsions for parenteral use should have droplet size less than 1 µm (generally
100–1000 nm), and hence are often called submicron emulsions, or (less properly)
nanoemulsions.

COMPONENTS OF EMULSIONS USED FOR PARENTERAL APPLICATIONS


A typical parenteral o/w emulsion is composed of lipid droplets (10–20%), emulsifier, and
osmotic
agent; it is administered by either intravenous (IV) bolus or IV infusion.

Table 10.1 summarizes the lipids most commonly used in parenteral emulsions. Long- and
medium-chain triglycerides (LCT and MCT, respectively), either alone or in combination, are
used in commercial parenteral emulsions owing to their long history of safety. LCT are
derived from vegetable sources such as soybean oil, safflower oil, sesame oil, and
cottonseed oil, whereas MCT are obtained by re-esterification of fractionated coconut oil
(mainly caprylic and capric fatty acid).
Surfactants

Surfactants are commonly used to stabilize the emulsion by reducing interfacial


tension between the oil and the water phases. Although a variety of surfactants are available,
only a few are used in approved parenteral emulsion products. The most commonly used
surfactant in parenteral products is phosphatidylcholine (PC). PC is a natural emulsifying
agent derived from egg yolk or soybean ‫صفار البيض أو فول الصويا‬. PC is commonly
called lecithin.
Fig.1 phosphatidylcholine (PC). Fig.2 phosphatidylcholine (PC).

The allowed concentration (after dilution) for administration for each of the
surfactants is listed in Table 10.2.
Other surfactants that have been used in parenteral products are synthetic nonionic
surfactants including Cremophor® EL (Polyoxyl-35 castor oil), Solutol HS-15
(polyoxyethylene- 660-hydroxystearate), Tween® 20, 40, and 80, Span® 20, and Poloxamer
188. Poloxamer 188 has been shown to be superior in stabilizing emulsion during autoclaving
compared to other surfactants (Jumaa and Muller, 1998).

Emulsion classification

 Oil in Water O/W Type


 Water in Oil W/O Type
 Multiple Emulsions
o O/W/O
o W/O/W

 Macroemulsion
 Microemulsion
 Nanoemulsion

Emulsion Instability
Emulsion Stability: Strong and Stable or Weak and Feeble

Other instability form (Phase inversion)


Stokes’ Law for settling (sedimentation) or creaming

Stokes’ Law states that the terminal velocity, V, in m/s, is given by:

 g is the gravitational acceleration (m/s2)


 ρp is the density of the particles (kg/m3)
 ρf is the density of the fluid (kg/m3)
 η is the continuous medium viscosity (Pa.s)
 R is the particle or droplet radius (m)
In the purpose to increase stability to avoid creaming and sedimentation

1-increased the viscosity of the dispersing phase

2-decreased the particle size

3-reduced the density difference between the two phases by increasing zeta potential.

Zeta potential

Zeta potential. Zeta or electrokinetic potential is related to the surface charge of the emulsion
droplets and it is generally measured by electrophoretic techniques. The zeta potential is
highly dependent on the surfactants used.

A charged drug molecule at the interface will also affect the zeta potential.

Zeta potential is measured using a Zetasizer Nano ZS (Malvern Panalytical) system which
calculates zeta potential using the principle of electrophoresis.

During a zeta potential analysis, charged colloidal dispersions are placed into a zeta cell and
upon application of an external electric field, the particles travel toward the electrode that has
a charge opposite to that of the particle. Their velocity, or electrophoretic mobility, under the
influence of an electric field, is measured using LASER Doppler velocimetry. It is then used
to calculate the zeta potential by applying the Henry equation:
By increasing zeta potential the particles repel each other‫ تتنافر‬, To overcome this
difficulty, we use an emulsifier (Surfactant).

What is a Surfactant?

A surfactant is a substance, that when added to water, reduces the surface tension of the
solution thus increasing its substrate wetting properties. At low concentrations, a surfactant
has the property of migrating and being adsorbed on the interfaces present in the system. It
alters the interfacial free energies of these interfaces. Thus, a surfactant is a surface-active
agent.

Surfactants can be referred to by a variety of terms: soap, wetting agent, dispersing agents,
substrate wetting additives, emulsifiers, surface-active agents, stabilizers, or solubilizers.
They are necessary for the wet stage of polymers and coatings. Chemists use surfactants to
change the composition of a liquid which enables specific properties that meet the needs for
market applications. Since surfactants can also cause detrimental effects in the film, such as
blisters, surfactant leaching, and less water resistance, chemists need to use the lowest levels
possible while maintaining the coating’s performance.

Four Types of Surfactants

There are four basic classes of surfactants: nonionic, anionic, cationic, and amphoteric. All
four types of surfactants can be utilized in pigment dispersions.

1. Nonionic Surfactants

Chemists use nonionic surfactants after polymerization to achieve stability, and then in
the grind for wetting and dispersing pigments and again in the letdown to achieve optimal
substrate wetting. Nonionic surfactants also help with stability of the formulation, heat age
stability, freeze/thaw resistance, and in-can stability.
With nonionic surfactants, chemists should consider the HLB values as well as a cloud
point. The HLB value plays a critical part in its functions and properties like emulsification,
solubility, wetting, and dispersion. The cloud point affects storage conditions and if the cloud
point is too low the coating may have phase separation and instability. For low-foam
applications, the cloud point of the product should be just below the application temperature.

HLB (Hydrophile-Lipophile Balance)

HLB value is an empirical expression for the relationship of the hydrophilic ("water-
loving") and hydrophobic ("water-hating") groups of a surfactant. The higher the HLB
value, the more water-soluble (hydrophilic) the surfactant. The HLB value of nonionic
surfactants is a measurement – on a scale of 1 to 20 – of the degree of water/oil solubility of a
given surfactant. The HLB of a particular surfactant is directly related to the structure of both
its hydrophilic and hydrophobic parts and plays a critical role in its function and properties.
To calculate HLB, take the molecular weight of the surfactant hydrophilic chain, divided by
the total molecular weight, and then multiply by 20.

HLB= [0-20] ;

HLB=0 highly lipophilic molecule (100%).

HLB= 20 highly hydrophilic molecule (100%).

2. Anionic Surfactants

Chemists use anionic surfactants during polymerization as primary and secondary


emulsifiers. They are used to control electrostatic stabilization and particle size. Unlike their
nonionic counterparts, anionic surfactants don’t have a theoretical HLB value or a cloud
point.

3. Cationic Surfactants

Chemists use cationic surfactants for their positive charge and anti-static properties.
Typically, we see cationic surfactants used in textiles for their fabric softening ability and
coatings for their anti-corrosive and anti-static properties.

4. Amphoteric Surfactants

Amphoteric surfactants are naturally cationic at low pH and anionic at high pH. They
are very mild and non-irritating when used in cleaners and detergents.
Applications for Surfactants
Emultion direction
 To formulate W/O emulsion we use emulsifier with weak HLB 3 to 6 enough.
These surfactants have lipophilic trait, i.e very soluble in the lipo phase.
 To formulate O/W emulsion we use emulsifier with strong HLB > 8.
These surfactants have hydrophilic trait, i.e very soluble in the hydro phase.

HLB value are additive


In general we use emulsifier mixture (hydrophilic, lipophilic…)

Final HLB= ([HLB emulsifier A * molar masse A] + [HLB emulsifier B * molar masse B])
Molar masse A+ Molar masse B

The HLB value of surfactants that provides the lowest interfacial tension between the
oil and water phases for a given lipid mixture is called the required HLB. Each of the
lipophilic ingredients used in an o/w emulsion has a required HLB value (e.g., 6–7 for
cottonseed oil and 14 for castor oil).

An emulsion is most stable when a surfactant or combination of surfactants has a


HLB value close to that required HLB value of the oil phase.

General formulation of emulsion

Oil………………………………….20%

Emulsifier 1

…………………5%

Emulsifier 2

Water…………………………QSP 100%.

We heat the oil and water at 70 °C, mixed with mechanical stirring.

Multiple emulsions (w/o/w)------Cosmetic use

1) Preparation of a simple emulsion.

2) Formulation of the second layer: Gradually add water to the simple emulsion plus
hydrophilic emulsifier, using gentle agitation.

To increase stability we add:

Electrolyte (MgSo4, NaCl)

Hydrophilic polymer (cellulose derivative)

Lipophilic gelling agent (fatty acid, wax).

N.B

The addition of two or more emulsifiers does not necessarily mean the formulation of a
multiple emulsion, but the goal is to have an additive HLB.

CHARACTERISTICS OF EMULSIONS

There are a number of physicochemical properties of emulsions that are important to consider
when developing an emulsion formulation for a drug. These include, but are not limited to,
particle (droplet) size, viscosity, osmolarity, and zeta potential, which are used to monitor the
physical stability of emulsions. Assays of potency and degradant levels are used to monitor
the chemical stability of emulsions.

Particle (droplet) size. An important parameter is the particle (droplet)


size of the emulsion. A variety of instruments and techniques exist for
monitoring particle size. The most
widely used techniques rely on laser light scattering, as reviewed by
Tadros et al. (2004).
Instrument manufacturers include Nicomp, Coulter, Horiba, Sympatec, and
Malvern.
Electron microscopy has also been used, but artifacts introduced by fixing
techniques
should be carefully controlled. Typically, emulsions produced by the
methods described
earlier yield particle sizes of 100–1000 nm; particle sizes less than 200
nm are generally
required for emulsions used intravenously.

Viscosity. This parameter can be monitored by standard rheological


techniques. The rheological properties of emulsions, reviewed by Sherman
(1983), can be complex, and depend on the identity of surfactants and oils
used, ratio of disperse and continuous phase, particle size, and other
factors. Flocculation will generally increase viscosity; thus, monitoring
viscosity on storage will be important for assessing shelf life.

Osmolarity. Osmolarity of a conventional emulsion is largely determined


by components of
the continuous phase, and the disperse phase may contribute little to the
osmolarity. Thus,
water-soluble excipients such as glycerol are frequently added to adjust
tonicity of emulsions intended for parenteral use. Conventional techniques
can be used for monitoring
osmolarity. Owing to possible changes in emulsion structure on freezing,
instruments that
rely on vapor pressure lowering are more suitable for monitoring
osmolarity of emulsions
than those based on freezing point depression.

Zeta potential. Zeta or electrokinetic potential is related to the surface


charge of the emulsion
droplets and it is generally measured by electrophoretic techniques. The
zeta potential is
highly dependent on the surfactants used.

Chemical stability. Certain emulsion components, especially those


derived from unsaturated
lipids, can give rise to undesirable degradation products on storage. These
can include oxidative products (e.g., lipid hydroperoxides and aldehydes),
which may impair drug stability.

 Controlling lipid peroxidation

The other important factor in retarding and controlling lipid peroxidation is


the use of
appropriate antioxidants, which can inhibit the pathway at various points
and stabilize lipids. The most useful are phenol-based antioxidants, for
example, butylated hydroxytoluene
(BHT), butylated hydroxyanisole (BHA), propyl gallate, and vitamin E
(α-tocopherol).
All of these form stable free radicals, thus acting as radical scavengers
and chain terminators. When using vitamin E, it is important to
remember that only the free phenol is active as an antioxidant; derivatives
such as vitamin E acetate or tocopherol polyethylene glycol (TPGS) will not
inhibit lipid peroxidation until metabolized. Other antioxidants (e.g.,
ascorbic acid, ascorbyl palmitate) act as oxygen scavengers, which
will prevent formation
of lipid hydroperoxides but not conjugated dienes. The two types of
antioxidants, by acting
at different points in the pathway, can act synergistically if used together
(Handbook of Pharmaceutical Excipients, 1994).

It should be noted that ascorbic acid derived oxygen scavengers are


also reducing agents, and in fact can promote rather than retard
peroxidation if metal ions are present (Sevanian and Ursini, 2000);
inclusion of a chelating agent such as ethylene diamine tetraacetic acid
(EDTA) in the formulation will prevent this and enhance the antioxidant
activity of ascorbates. Use of ascorbates with drugs sensitive to reducing
agents should be avoided.

Physical stability. As indicated earlier, conventional emulsions are


inherently unstable from
a physical standpoint. Poor physical stability is ultimately exhibited by
phase separation,
which can be visually monitored. Certain properties of the emulsion will
start to change
long before this separation is visually apparent. An increase in particle size
is particularly
indicative of physical instability, since this monitors the coalescence or
flocculation that
is part of the process involved in ultimate phase separation. Increases in
viscosity (due to
flocculation) and changes in zeta potential (arising from a decrease in
droplet surface area)
are both indicative of poor physical stability. The presence of drug and
cosolvents can
potentially hasten the phase separation.

Emulsions, Microemulsions, and


Lipid-Based Drug Delivery Systems
for Drug Solubilization and Delivery
Part II: Oral Applications.
INTRODUCTION
Owing to the large increase in the number of water-insoluble
drugs in clinical development, lipids have come to the forefront as a
formulation and drug delivery tool, particularly for drugs that exhibit
dissolution rate-limited absorption.

Most frequently lipid-based drug delivery systems (LBDDSs) for


oral use are designed to present a poorly soluble drug in a solubilized form
to eliminate dissolution of crystalline material as the rate-limiting step to
absorption (Pouton, 2000). For poorly aqueous-soluble drugs, the
dissolution rate can be extremely low under physiological conditions,
leading to poor oral bioavailability and nonlinear exposure with increasing
dose (Hörter and Dressman, 1997).

Many of these lipophilic drugs will also exhibit a strong food effect
where the bioavailability increases due to the solubilizing effects of
ingested food and concomitant excretion of bile (Charman et al., 1997;
Fleisher et al., 1999). By introducing the drug in solubilized form,
lipid-based formulations have the potential to increase
bioavailability and eliminate the food effect.
Emulsifiers
Often lipid-based oral formulations contain emulsifiers (surfactants) to facilitate dispersion of
the drug and formulation components after ingestion. Surfactants can be classified according
to their hydrophilic–lipophilic balance (HLB) number (Griffin, 1949);

Article Quote Example


Preparation and characterization of sodium caseinate/ xanthan gum complexes in acidic conditions and their

use for the stabilization of oil-in-water emulsions Houria Bouziane1 | Soumia Seddari2 | Fatiha Boudjema3 |

Nadji Moulai-Mostefa.

The main objective of the present study was to examine the possibility of
formulating stable acid O/W emulsions using NaCn/XG complexes
prepared at pH 4. The stability of emulsions can be enhanced by using the
electrostatic interactions between PR and PS. For this, two approaches
were proposed; one of them is called the “layer by layer” training method.

N.B
XG, Xanthan gum = polysaccharides (PS)…

This gum is produced artificially by the pure culture fermentation of


the bacterium Xanthomonas campestris on glucose. It, like cellulose,
consists of 1,4-β-glycosidically linked chains of glucose with, additionally, trisaccharide side-
chains on alternating anhydroglucose units.

Sodium caseinate (NaCn) = Proteins (PR)

Proteins (PR) and polysaccharides (PS) are among the most used biopolymers for the
replacement of synthetic surfactants (Silva et al., 2015). The stabilization of emulsions by PR
alone or in combination with PS has been the objective of several previous works (Perugini et
al., 2018; Seddari et al., 2022). The complexation between PR and PS has also been studied
because of the benefits that can bring in the stabilization of dispersed systems when carried
out under appropriate conditions (HadjSadok et al., 2010; Jones et al., 2011; Warnakulasuriya
& Nickerson, 2018). It has been observed that most often, the complexation between PR and
PS macromolecules results from a non-covalent association, mainly due to attractive
electrostatic interactions (Albano et al., 2019; Dai et al., 2022).

Sodium caseinate (NaCn) which is the major protein in milk, can be used as a natural
emulsifier for the formulation of oil-in-water (O/W) emulsions owing to its amphiphilic
properties (Tavasoli et al., 2022).

However, emulsions stabilized by NaCn are unstable at pH near to its isoelectric point (pI 4.6)
due to the reduction of electrostatic repulsion between oil droplets (Perugini et al., 2018).
There are many pharmaceutical forms especially topical ones that are
prepared at acidic pH (Angelova-Fischer et al., 2018; Blaak et al., 2017; Kilic et al., 2019).

Acid food emulsions based on the whey protein isolate/xanthan gum complex have also been
successfully formulated (Matsuyama et al., 2021). They are manufactured and distributed at a
pH close to 4. Therefore, it would be interesting to study the possibility of formulating stable
emulsions with NaCn under acidic conditions.

Complexation of PR with some anionic PS through electrostatic interactions can significantly


improve the stability of emulsions (Guzey & McClements, 2007). In the case of NaCn, adding
a PS such as xanthan gum (XG) can strengthen the protein network formed at the oil interface
(Seddari & Moulai-Mostefa, 2015). In pharmaceutical, XG is employed as a stabilizing agent
in oral and topical formulations (Singhvi et al., 2019), for the production of extended-release
matrix tablets (Fan et al., 2008), or for its mucoadhesive properties (Laffleur et al., 2016).
Several works were devoted to the evaluation of the properties of NaCn/XG dispersions at
acidic pH (Gravelle et al., 2021; Hidalgo et al., 2016; Liu et al., 2012).
Cosolvents

Hydrophilic cosolvents (e.g., ethanol, propylene glycol, polyethylene glycol


400 [PEG 400])
may be used in lipid-based oral formulations if needed to improve drug
solubilization. These
hydrophilic components may also aid dispersion by facilitating ingress of
water into the formulation. An important advantage of lipid-based systems
with a co-solvent over formulations consisting only of cosolvents is that
after dissipation of the hydrophilic components, the lipids will remain to
prevent drug precipitation, whereas in the absence of lipids, drug
precipitation is likely.

Self-emulsifying drug delivery systems ‫أنظمة توصيل األدوية ذاتية االستحالب‬

Self-emulsifying drug delivery systems (SEDDSs) are oral dosage forms consisting of drug,
oils, surfactants, and sometimes cosolvents (Constantinides, 1995; Pouton, 1997; Pouton,
2000). On addition to water (or on introduction to the gastrointestinal [GI] tract) and with
gentle agitation, the system will easily form an emulsion or microemulsion (defined in the
following).
Selfemulsification may be driven by several mechanisms (López-Montilla et al., 2002). The
mechanisms most likely involved in dispersion of pharmaceutical formulations are diffusion
and stranding, those driven by osmotic pressure imbalances (Greiner and Evans, 1990), phase
transformations, and changes owing to alteration of environmental conditions (e.g., pH). If the
droplet size after dispersion is substantially less than 1 micron, the SEDDS is often designated
as a selfnanoemulsifying drug delivery system (SNEDDS).

Published study example Ref. Self-double-emulsifying drug delivery system (SDEDDS): A new way for oral delivery of drugs with
high solubility and low permeability Xiaole Qi, Lishuang Wang, Jiabi Zhu ∗, Zhenyi Hu, Jie Zhang.

The present studies have clearly demonstrated the potential utility of SDEDDS for
formulating pidotimod (Pidotimod is an immunostimulant) with sustained release in vitro
and improved oral bioavailability in vivo. The optimal formulation of the pidotimod-
SDEDDS (F4) was successfully developed. The SDEDDS readily released the lipid phase to
form fine water-in-oil-in-water double emulsions, with a sustained release of pidotimod.

Pharmacokinetic studies in rats revealed that the absorption of pidotimod from SDEDDS
showed 2.56-fold increase in bioavailability as compared to the same oral dose (80 mg/kg) of
the pidotimod aqueous solution. Moreover, the SDEDDS were found to be stable over a
period of 6 months under 25 ◦C. Our studies illustrated the potential use of novel self-double-
emulsifying drug delivery systems for oral delivery drug with high solubility and low
permeability.
low permeability Xiaole Qi, Lishuang Wang, Jiabi Zhu ∗, Zhenyi Hu, Jie Zhang.
Ref. Self-double-emulsifying drug delivery system (SDEDDS): A new way for oral delivery of drugs with high solubility and

PHASE BEHAVIOR AND COMPLEX FLUID STRUCTURES

Before reviewing the steps for design of LBDDSs, it is necessary to have a


brief review of the
phase behavior of these systems and utility of phase diagrams. Mixtures of
oil, water, and surfactant are known to create a variety of microstructures
depending on the relative proportion of each component (Gelbart and Ben-
Shaul, 1996).

The various structures formed are the result of the amphiphilicity of the
surfactant whose hydrophilic domain and lipophilic domain drive it to the
interface of oil/water systems. These phases include the well-organized
structure of lamellar, hexagonal and cubic liquid crystals, the water
continuous L1 phase, which includes micelles and o/w microemulsions,
and the oil continuous L2 phase, which includes inverse micelles and w/o
microemulsions (Figure 11.6).

The L1 (micelle/microemulsion) and L2 (water-in-oil microemulsion/


isotropic oil continuous phase) phases are those most often encountered in developing
LBDDSs.
SOLUBILIZATION

Drug candidates for lipid-based drug delivery are poorly aqueous- soluble and
lipophilic (typically log P > 3). Being a poorly soluble drug alone is not sufficient, as
solubility in the lipid components for LBDDSs is required. Initiating development of an
LBDDS will begin with a solubility screening study in select lipid excipients, emulsifiers, and
cosolvents (e.g., ethanol, propylene glycol, PEG 400). The primary solvent will typically be
an alkylglyceride, and cosolvents are used to increase the solubility in the blend.

Hydrophobic non-ionizable drugs (generally characterized by a (Log Poctanol/water


>3) may be solubilized by long-chain triglycerides (LCT) or medium chain triglycerides
(MCT) and/or by combination of a lipid with a low HLB surfactant such as
phosphatidylcholine/medium chain triglyceride or oleoyl macrogolglycerides. Less
hydrophobic drugs (viz., Log Poctanol/water <3) may be solubilized by monoglycerides or
propylene glycol monoesters, or by combinations of these lipids with high HLB surfactants or
hydrophilic co-solvents. Often a combination of low HLB and high HLB surfactants give
superior solubilization, which may also optimize the dispersion properties described later.

TOXICOLOGICAL CONSIDERATIONS FOR ORAL


LIPID-BASED DRUG DELIVERY SYSTEMS (LBDDSs)

Compared to parenteral formulations, toxicity is rarely a concern for oral lipid-based


formulations. Most lipids discussed here are considered generally recognized as safe (GRAS);
indeed, long-chain tri-, di-, and monoglycerides are absorbed from foods in greater quantities
than those administered in pharmaceutical dosage forms. Although there are reports that
MCTs can accelerate small bowel transit time and induce diarrhea (Verkijk et al., 1997),
dietary consumption of up to 1 g/kg of MCTs has been shown to be safe in human clinical
trials (Traul et al., 2000). Toxicity of surfactants used in lipid-based formulations varies;
levels should be kept within reported acceptable limits. In addition to toxicology, for lipid
formulations administered orally as liquids, specialized efforts from the standpoint of taste,
flavor and mouth feel must be considered.

Formulation material

magnetic stirrer
homogenizer (Ultra-turrax T-25, IKA, Germany)

Rheology Material

Tensiometer
Anton Paar Modular Compact Rheometer MCR 302.
Microprocessor pH/ion Meter pMX 2000 (WTW, Germany).

LF 191 conductimeter (WTW, Germany)

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