LECITHIN Yu. A. Shchipunov Russian Academy of Sciences, Vladivostok, Russia Lecithin is a most prominent member among the surfac- tants. It has a long history of use, dating back in antiquity. The ancient Greeks e.g., treated leather with dried egg yolk, which contains up to 30 wt% lecithin, to remove fats and oils, making it softer. At present time it is used in every day life and in many fields, including foods, animal feeds, pharmaceuticals, cosmetics, and a variety of indus- trial applications. Lecithin is also one of the most popular substances studied by academic scientists. The strong in- terest in it and widespread use can be explained at least by three main reasons; 1) lecithin can be found in any living matter because it is one of the main constituents of the lipid matrix of the biological membranes, 2) it is a bio- compatible naturally occurring surfactant, and 3) it pos- sesses varies functionalities. Lecithin in solutions forms micelles and liposomes, self-organizes into liquid-crystal- line structures, disperses and stabilizes dispersions, and provides wetting and coats surfaces, inducing their mod- ification. Its properties and properties of self-organized structures have been and are still under intensive inves- tigations. There are thousands of publications concerning lecithin. The framework of a short review does not allow discussing all its properties and structures in sufficient details. Therefore, the article should be taken as an intro- duction to the colloid chemistry of lecithin. The discussion of the main subject is preceded by a consideration of no- menclature, structure, sources, composition, and process- ing, and it is accomplished by a description of numerous field of lecithin application. NOMENCLATURE, STRUCTURE, SOURCES, COMPOSITION, AND PROCESSING Lecithin is a trivial name for 1,2-diacyl-sn-glycero-3- phosphocholine (1). It was usually applied to a crude mixture of phospolipids and tracylglycerols obtained as a by-product upon refining of seed oils. Although the IUPAC-IUB Commission did not recommend, the trivial name is widely used in the academic literature to designate a purified substance from natural sources. But initially, the term was suggested by Maurice Gobley. He derived it from the Greek word lekithos for egg yolk, from which the le- cithin in the form of a sticky, orange-colored material was isolated as early as 1850 (2). Lecithin belongs to the phosphoglycerides (1, 3–6). This class of substance are based on diacyl derivatives of 3-glycerophosphoric acid (see Fig. 1) A choline is joined in an ester linkage to the second hydroxyl group of the phosphoric acid residue that gives 1,2-diacyl-sn-glycero- 3-phosphocholine, called often phosphatidylcholine (PC). The last-mentioned term includes ‘‘phosphatidyl’’ in place of ‘‘1,2-diacyl-sn-glycero-3-phospho.’’ Phosphoglycer- ides are also named in the literature as glycerophospho- lipids. This name stresses that they are among phospho- lipids (PLs), i.e., among the class of substances that have a phosphate group, and relate to lipids—a wide range of compounds containing, as suggested by Gunstone (5), ‘‘fatty acid residues or closely related compounds such as the corresponding alcohols and the sphingosine bases.’’ It would be well to mention other major PLs. They differ from lecithin, as obvious from Fig. 1, by the end functional group replacing the choline. Sometimes one fatty acid residue in a lecithin molecule is absent, that gives a monoacyl form, known as lysolecithin. Noteworthy also are phosphocholine-containing PLs, of which the ba- sic backbone of the molecule is presented by a long-chain aminodiol, sphingosine (Fig. 1), instead of glycerol. They are usually called sphingomyelin. The sphingolipids are among the major naturally occurring PLs, being some- times as alternative to lecithin in animal (mainly nervous) tissues (6, 7). The structural formula of lecithin in Fig. 2 is a steric representation in the Fisher projection of the glycerol de- rivatives. As suggested by the IUPAC-IUB Commission (8), the top carbon atom of a vertically oriented glycerol chain is designated as C-1 and the rest atoms as C-2 and C-3. The prefix sn (stereospecifically numbered) imme- diately ahead of the term ‘‘glycerol’’ in the name of the substance is indicative of such numbering. Although two fatty acid residues in a lecithin molecule appear as an interchangeable, they are not, however, equivalent from L Encyclopedia of Surface and Colloid Science 2997 Copyright D 2002 by Marcel Dekker, Inc. All rights reserved.
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LECITHIN
Yu. A. ShchipunovRussian Academy of Sciences, Vladivostok, Russia
Lecithin is a most prominent member among the surfac-
tants. It has a long history of use, dating back in antiquity.
The ancient Greeks e.g., treated leather with dried egg
yolk, which contains up to 30 wt% lecithin, to remove fats
and oils, making it softer. At present time it is used in
every day life and in many fields, including foods, animal
feeds, pharmaceuticals, cosmetics, and a variety of indus-
trial applications. Lecithin is also one of the most popular
substances studied by academic scientists. The strong in-
terest in it and widespread use can be explained at least by
three main reasons; 1) lecithin can be found in any living
matter because it is one of the main constituents of the
lipid matrix of the biological membranes, 2) it is a bio-
compatible naturally occurring surfactant, and 3) it pos-
sesses varies functionalities. Lecithin in solutions forms
micelles and liposomes, self-organizes into liquid-crystal-
line structures, disperses and stabilizes dispersions, and
provides wetting and coats surfaces, inducing their mod-
ification. Its properties and properties of self-organized
structures have been and are still under intensive inves-
tigations. There are thousands of publications concerning
lecithin. The framework of a short review does not allow
discussing all its properties and structures in sufficient
details. Therefore, the article should be taken as an intro-
duction to the colloid chemistry of lecithin. The discussion
of the main subject is preceded by a consideration of no-
menclature, structure, sources, composition, and process-
ing, and it is accomplished by a description of numerous
field of lecithin application.
NOMENCLATURE, STRUCTURE, SOURCES,COMPOSITION, AND PROCESSING
Lecithin is a trivial name for 1,2-diacyl-sn-glycero-3-
phosphocholine (1). It was usually applied to a crude
mixture of phospolipids and tracylglycerols obtained as a
by-product upon refining of seed oils. Although the
IUPAC-IUB Commission did not recommend, the trivial
name is widely used in the academic literature to designate
a purified substance from natural sources. But initially, the
term was suggested by Maurice Gobley. He derived it from
the Greek word lekithos for egg yolk, from which the le-
cithin in the form of a sticky, orange-colored material was
isolated as early as 1850 (2).
Lecithin belongs to the phosphoglycerides (1, 3–6).
This class of substance are based on diacyl derivatives of
3-glycerophosphoric acid (see Fig. 1) A choline is joined
in an ester linkage to the second hydroxyl group of the
phosphoric acid residue that gives 1,2-diacyl-sn-glycero-
3-phosphocholine, called often phosphatidylcholine (PC).
The last-mentioned term includes ‘‘phosphatidyl’’ in place
of ‘‘1,2-diacyl-sn-glycero-3-phospho.’’ Phosphoglycer-
ides are also named in the literature as glycerophospho-
lipids. This name stresses that they are among phospho-
lipids (PLs), i.e., among the class of substances that have a
phosphate group, and relate to lipids—a wide range of
compounds containing, as suggested by Gunstone (5),
‘‘fatty acid residues or closely related compounds such as
the corresponding alcohols and the sphingosine bases.’’
It would be well to mention other major PLs. They
differ from lecithin, as obvious from Fig. 1, by the end
functional group replacing the choline. Sometimes one
fatty acid residue in a lecithin molecule is absent, that
gives a monoacyl form, known as lysolecithin. Noteworthy
also are phosphocholine-containing PLs, of which the ba-
sic backbone of the molecule is presented by a long-chain
aminodiol, sphingosine (Fig. 1), instead of glycerol. They
are usually called sphingomyelin. The sphingolipids are
among the major naturally occurring PLs, being some-
times as alternative to lecithin in animal (mainly nervous)
tissues (6, 7).
The structural formula of lecithin in Fig. 2 is a steric
representation in the Fisher projection of the glycerol de-
rivatives. As suggested by the IUPAC-IUB Commission
(8), the top carbon atom of a vertically oriented glycerol
chain is designated as C-1 and the rest atoms as C-2 and
C-3. The prefix sn (stereospecifically numbered) imme-
diately ahead of the term ‘‘glycerol’’ in the name of the
substance is indicative of such numbering. Although two
fatty acid residues in a lecithin molecule appear as an
interchangeable, they are not, however, equivalent from
L
Encyclopedia of Surface and Colloid Science 2997Copyright D 2002 by Marcel Dekker, Inc. All rights reserved.
the stereochemical point of view (6). This difference re-
veals itself in natural lecithins, which bear usually satu-
rated acids at the sn-1 position and unsaturated ones at sn-
2 position (6, 9). Moreover, there are phospholipases A1
and A2 in the living cell that cause a selective cleavage
of either the C-1 ester or the C-2 ester linkages, respec-
tively (10, 11), thus demonstrating the stereochemical
asymmetry of the native PLs.
The phosphocholine residue contains oppositely
charged groups, while the lecithin possesses a zwitterionic
character. A pK for a choline residue is near 13,9, while
for the phosphate group it is below 2 (6, 12, 13). Therefore,
the lecithin molecule has a net neutral charge over about
the entire pH range.
The PLs form the lipid matrix of biological membranes
and membranous organelles (14). Their total amount va-
ries from 5 to 60%, among which lecithin frequently
accounts for 50–60% (7, 15–18). In view of the fact
that the biological membranes are the basic structural
element of the cell, the lecithin can be found almost in
any living matter.
Commercial lecithin is a complex mixture of PLs
shown in Fig. 1 as well triglycerides, fatty acids, and
carbohydrates (7, 16–19). The exact composition depends
on the source of the lecithin as well as on the method of
extraction and purification (18, 20–23). Table 1 provides
representative data on the lecithin distribution in some
species that demonstrates a variability of PL content even
from organ to organ. In addition, there are notable dif-
ferences in the fatty acid residues. Illustrative examples
for fatty acid composition of lecithins separated from
industrially important sources are given in Table 2. Al-
though lecithin can be found, as mentioned previously, in
all kinds of living matter, it is predominantly manufac-
tured from plant seeds, mainly from soybean oilseeds and
to a lesser degree from cottonseeds, peanut, sunflower,
and rape seeds (7, 17, 23). From animal sources, egg yolk
Fig. 1 General structural formulas for phospholipids.
Fig. 2 General formula for lecithin presented in a Fischer
projection.
2998 Lecithin
and brain tissues (bovine brain) are primarily used (16,
23, 24).
Lecithin from plant sources is commonly obtained as a
by-product at a pretreatment stage of the oil refinement.
The technological process is based on the hydration of
PLs after an addition of water into oil and their subse-
quent precipitation in the gumlike form . That is why the
stage is known as degumming (20, 22, 23). The water
amount needed to remove PLs is approximately equal to
their content in the oil (2–3 wt% in soybean oil). The
degumming is performed at 60–75�C during 0.5–1.0 h if
it is a batch process (20–23). On separating the precipi-
tated gum by means of the centrifuge, one will have a
fatty-like mass, from light brown to yellow or reddish
brown in color. This is a mixture of PLs containing in
accordance with a various published data 12–46% leci-
thin, 8–34% PE, 1.7–21% PI, 0.2–14% PA, 0.2–6.3%
PS, and 1.5–8.5% lysolecithin (see Fig. 1) (5, 9, 17–20,
22). Then pure PLs can be obtained by fractionation and/
or separation of the initial crude lecithin (6, 20, 22, 23). It
can be also modified by means of chemical or enzymatic
treatment to have a mixture with desired properties (18,
19, 23, 33–37).
Lecithin from animal sources—mainly from egg yolk
and to a lesser degree from brain tissues—is not manu-
factured as the by-product. The technological processes
differ from previously described ones owing to tight bind-
ing of PLs with proteins. To separate them, the extraction
by means of such polar solvents as alcohols (ethanol or
iso-propanol) and ethyl acetate is often applied (16, 22–
24). A mixture of PLs thus obtained from egg yolk is
enriched with lecithin in distinction to vegetable products.
It can be contain, as reported by various authors (16), 66–
87% lecithin as well as 8–24% PE, trace to 3% PS, 1–6%
SM, and 2.5–6% lyso-PLs (18, 22–24). The egg lecithin
has a higher price than the soybean one, and hence is
mainly used in pharmaceuticals.
The living systems possess remarkably constant lipid
composition that is rather resistant to a change in envi-
ronmental conditions and diet. Results with the improve-
ment of dietary quality of the yolk egg of the domestic
hen for human consumption can provide an illustrative
example. There was an idea to produce ‘‘polyunsaturated
low-cholesterol eggs’’ by dietary and genetic means. Nu-
merous attempts showed that the initial optimism was
premature. The diet led to some changes in the lipid com-
position and cholesterol content, but it proceeded in a
compensatory manner (24). For instance, the reduction of
cholesterol was accompanied, as shown by Kudchodhar et
Table 2 Fatty acid composition of lecithins from commercial sources
Lecithin
Residuea
16:0 18:0 18:1 18:2 18:3 20:4 22:6 24:4
Egg yolkb 67/0 26/0 5/51 0/24 — 0/7 0/4 0/4
Bovine brainc 55/25 22/0 8/49 — — 0/11 — —
Bovine liverd 18/8 33/0 2/21 — — 0/10 — —
Soybean oile 34/1 8/2 8/5 43/5 5/7 — — —
aValues are expressed as mol%. The first number in columns shows the amount of fatty acid residue in sn-1 position, the second in sn-2 position; the acids
with an amount is < 2 mol% are not shown or are taken equal to zero.b(From Ref. 24.)c(From Ref. 32.)d(From Ref. 16.)e(From Ref. 9.)
Table 1 Lecithin distribution in various organs of different
species
Organ
Skeletal
Species Heart Liver Lung Kidney muscle Brain
Human 40.0c 43.6c 50.4a 33.1g 53.9a 29.2a
Bovine 40.7a 54.0a 39.5e 33.8a 42.5c 29.6a
Sheep 25.5c 39.7c 58d 35.8c — 37.3c
Mouse 40.6e 45.6c 49.4a 35.6g 55.9a —
Rat 36.0e 54.6f 57.5h 34.3g 51.1e 36.8e
Frog 39.6e 46.5g 46.5a 34.3g 55.2e 45.0b
Lobster — — — — 55.7a 58.4a
Values are percentage of total PLs.a(From Ref. 25.)b(From Ref. 26.)c(From Ref. 27.)d(From Ref. 28.)e(From Ref. 16.)f(From Ref. 29.)g(From Ref. 30.)h(From Ref. 31.)
L
Lecithin 2999
al. (38) and Clarenburg et al. (39), by an absorption of ste-
rols from feeding plants that gave only marginal success.
A genetic selection has not also allowed realizing the de-
sired improvement of the lipid and cholesterol compo-
sition for the egg yolk of the domestic hen. This is ex-
plained why the PLs produced from the same natural
sources collected from place to place on the Earth de-
monstrates a low variability in their chemical composition
and physico-chemical properties. This uniformity has the
great importance for the industrial applications and scien-
tific research.
PHYSICO-CHEMICAL AND COLLOIDPROPERTIES IN SOLUTIONS
Lecithin is soluble or dispersal practically in all solvents
including aliphatic, halogenated, and aromatic hydrocar-
bons, alcohols, esters, and ethers, water, and aqueous so-
lutions (3, 12, 23, 40). The one exception is presented by
acetone and a number of ketones. Acetone is widely app-
lied to precipitate lecithin from solutions and/or separate it
from acetone-soluble substances (e.g., triglycerides), pro-
viding a convenient method for its purification (20–23).
Lecithin is prone to self-organize into various colloid
structures in its solutions. This depends strongly on the
type and nature of solvent. Furthermore, the presence of
impurities or other PLs, as in commercial samples, causes
significant change of phase behavior and properties of
formed structures. It is often used in practice. More than
40 various formulations are suggested by manufactures
for different applications (19–23). This article is mainly
devoted to pure lecithin. The common approaches used to
develop formulations will be considered at the end.
Binary Systems
Lecithin-water
Lecithin is insoluble in water. It can be only dispersed (3,
12–42, 40–42). Lecithin forms true solutions at very
small concentrations because of its strong liability for
self-assembling into aggregates. For example, the critical
micelle concentration (cmc) for dipalmitoylphosphatidyl-
choline is equal to 4.6 � 10�10 mol/dm3 (43). A shorten-
ing of each of both the fatty acid residues by one meth-
ylene group results in increase of the cmc in about one
order of magnitude. For instance, the cmc values for leci-
thin containing C8-,C7-, and C6- hydrocarbon chains are
equal to 0.2–0.3, 2, and 15 mM, respectively (44). A
detailed study performed by Marsh and King (45) showed
that the cmc does not change so sharp with the hydro-
carbon chain length. They suggested the following ex-
pression ln[cmc] = � 0.4–1.7nC for a dependence of the
critical micellar concentration on the number of carbon
atoms nC in the fatty acid residues.
Micellar aggregates, however, are not common for
naturally lecithin in the aqueous solutions. It usually self-
organizes into liquid-crystalline structures (3, 12, 40–42).
The binary phase diagram combined for soybean and egg
yolk lecithins is presented in Fig. 3. One can see that the
lameller liquid-crystalline mesophase La is predominant
for both the lecithins. The La mesophase consists of
bimolecular layers in which the molecules are oriented
with their hydrocarbon radicals toward the inside, while the
polar groups cover both the opposite surfaces (3, 41, 46–
48). Its schematic drawing is also given in Fig. 3. Water
molecules surround the functional groups as a hydration
shell and fill interlayers, thus separating the lamellae. The
bimolecular layer has a thickness varying between 4 and 6
nm. A lecithin molecule can occupy an area from 0.6 up to
1.0 nm2 (3, 41, 46, 48). The parameters of a bimolecular
layer depend on the fatty acid residues in the PL molecule
and water amount introduced. When being successfully
added to lecithin, water is absorbed by lamellae that causes
a change of their parameters; the thickness is decreased,
while the area occupied by 1 a lecithin molecule is in-
Fig. 3 Binary phase diagrams for egg yolk and soybean leci-
thins. The latter is shown by dashed lines. As obvious, the main
naturally occuring lecithins are not much different from each
other in the phase behavior. Insets present schematic represen-
tations of the liquid crytalline states. Their notations are made in
accordance with Luzzati suggestion. (From Ref. 40.)
3000 Lecithin
creased (3, 40). This has an important consequence. Be-
cause of the opposite change in the thickness and molecular
area with the water addition, the lecithin molecules holds
its cylindrical shape that makes the La mesophase stable
over a wide range of concentrations (49).
The La mesophase is of fundamental importance for
lecithin. The bimolecular layer is the basic structure of
vesicles (liposomes) (15, 41, 48, 50). As obvious from the
phase diagram (Fig. 3), lecithin forms a homogeneous
lamellar phase at a water concentration ranging from 7 to
10 wt% up to ca. 45 wt%. At a higher concentration, there
is a two-phase system in which the La mesophase coexists
with an aqueous solution. This is a region for vesicle
(liposome) formation. If a dried lecithin is placed in an
excess of water, it swells, forming characteristics cylin-
drical structures called myelin figures (3, 40, 51). The
process is illustrated by a set of pictures in Fig. 4. The
myelin figures were first described by Virchow in 1854
(51). Their formation is caused by expulsion of bimole-
cular lamellae from the bulk owing to the swelling. This
explains why the myelin figures are composed of coa-
xially arranged bimolecular layers (52–54). The process
is terminated by disintegration of the myelin figures into
spherical and oval particles. They stand for multilamellar
vesicles of which the structure can be represented as a
spherical particle with an inner aqueous core surrounded
by a shell made up of numerous closed bimolecular la-
yers. Oligolamellar—the shell consists of layers—and
unilamellar vesicles can be prepared from the multila-
mellar ones by means of mechanical treatment, e.g., so-
nication (41, 45). Their size varies between 0.01 and 100
mm, which depends mainly on the method used for the
visicle preparation (40, 41, 55). The thickness of a la-
mellae each involved into the shell is rather constant and
equal to about 40–50 nm.
It is worth mentioning that the fast uptake of lecithin
vesicles takes place in vivo by the cells of the mono-
nuclear phagocytic and reticuloendothelial systems when
they are introduced intravenously. To avoid it, lecithin is
modified or the vesicle surface is protected by introducing
various substances (see, e.g., Refs. 56, 57; some details
are considered in Polymer-lecithin complexes section).
Other liquid crystalline mesophases are formed at con-
centrations of water in lecithin < 10 wt% (Fig. 3). They
are also mainly among the lamellar type (Lb or Pb) (47).
The nonlamellar (hexagonal HII and cubic Qa) meso-
phases exist at higher temperatures ( > 90�C). The meso-
phase La transfers into Qa and then into HII with heating.
The transition from bimolecular to nonlamellar states is
brought about by a difference in the expansion of the
polar and nonpolar regions of molecules (41, 47). The
thermal activation leads to a change in hydrocarbon chain
conformations owing to trans-cis transition along C-C-C
chains. As a result, the nonpolar part of the bimolecular
layer expands more with heating than the polar region,
which leads to a change from the cylindrical shape of mo-
lecules to a conical one.
Lecithin shows a strong affinity for water (40, 58).
Dried samples are capable of absorbing water vapor. Up
to 20 or 21 water molecules per lecithin molecule can be
attached (59). This depends on the air humidity. The ab-
sorbed solvent forms a hydration shell of the polar region.
The whole hydration shell can include from 33 to 39 wa-
ter molecules (3, 60, 61), but it is completed only after
the direct contact of lecithin with water.
The hydrating water is normally subdivided into four
types (40, 58, 60). The first one or two absorbed H2O
molecules are called ‘‘inner’’ or ‘‘strongly bound’’ water.
They are linked so strongly with lecithin that they cannot
easily removed when it is dried. The following portion
forms a basic hydration shell around the polar region of
the lecithin molecule. It can include 5 to 11 solvent mol-
ecules. This type is known as ‘‘bound’’ water because of
its reduced mobility. The next type, termed ‘‘included’’ or
‘‘trapped’’ water, comprises 4 to 11 molecule. The rest of
the H2O is located in the outer part of the hydration shell,
filling mainly an aqueous interlayer between the bimole-
cular layers. When beginning the absorption, the first 3–5
solvent molecules are bounded with a phosphate group of
a lecithin molecule (Figs. 1 and 2) by means of hydrogen
bonds (40, 60, 62, 63). The following added water mole-
cules are attached to carbonyl groups and then form a
shell around a choline group.
The hydration of lecithin proceeds through few stages
(64). The absorption of the first water molecules, which
are attached to the phosphate group of the lecithin mole-
cule, takes place in a rather short time interval, less than a
minute. With filling the hydration shell, the rate of pro-
cesses becomes progressively slower. At the end stage, it
can reach up to ca. 1 h.
Lecithin-organic solvent
Lecithin is soluble, as mentioned above, in the most or-
ganic solvents. By self-organized lecithin structures, they
can be subdivided into two main types (40). The first one
is represented by organic solvents in which lecithin can
dissolve, forming true solutions and reverse micelles at
larger concentrations. This is the largest group. The sec-
ond type comprises solvents of which molecules form
numerous hydrogen bondings in the bulk. Lecithin are
capable of self-assembling in such the media, much like
in water, into liquid crystalline structures, demonstrating
lyotrophic mesomorphism.
L
Lecithin 3001
Reverse micelles: The inner volume of aggregates is
occupied by polar groups of lecithin molecules, while the
hydrocarbon chains are directed outward. The cmcs for
lecithin in benzene and n-decane are around 10 (65) and 3
(66) mM, respectively. The aggregation numbers for some
solvent media are presented in Table 3. There is rather
Fig. 4 Different stages of soybean lecithin swelling in water (A, F) and water-glycerol (30–70 v/v %) mixture (B–E) as it is observed
under the polarizing microscope. Glycerol was added to slow down the process. Photographs A–C show various types of myelin
figures. They were taken within 7 min (A), 25 min (B), and ca. 3 h (C) after a dried lecithin sample was brought into a contact with a
solvent. The myelin figures developed in water (A) are normally thinner than those obtained in the water-glycerol mixtures (B, C). The
vertical arrow in (C) marks helical myelin figures observed at an advanced stage. (D–F) Succeding stages of swelling. The beginning of
disintegration of myelin figures is presented in (D). The texture called "oily streaks" is seen in (E). This is typical of liquid crystals
possessing a well-organized lamellar structure. The closing stage is illustrated by a picture of vesicles (F). They can be obtained only
when a sample is placed in an excess amount of water. The vesicles seen with the polarizing microscope look like spherical particles
intersected with perpendicular dark lines (a cross). The appearance of the myelin figures after the contact of a solid substance with a
liquid is evidence that it is the La mesophase. This test is simple to perform, but it shows or confirms that the substance has multilamellar
structure (see the inset in Fig. 3) at these conditions. To make the presented photograhs, a small amount of dried lecithin and one or two
drops of water or its mixture with glycerol were placed on a glass plate and then covered with another one. The microscopic
observations were performed by a Carl Zeiss polarizing microscope equipped with a camera. Magnification � 100.
3002 Lecithin
wide scatter in the data, as seen for benzene solutions, ob-
tained by various authors. The reason might be in the
noncooperative nature of lecithin aggregation, which is
the common case when the surfactants self-assemble in
nonpolar media (67). In addition, the presence of even
trace amounts of water in organic solvents could strongly
influence the micellization (12, 40, 68). These factors
usually hinder the right determination of the aggregation
parameters.
There was made an attempt by Elworthy et al. (69) to
relate the micelle formation by lecithin to the dielectric
constant of organic solvents. The idea was based on expe-
riments in which mixtures of benzene with ethanol were
used. It was found that lecithin did not form micelles at
the dielectric constant equal to 29.0. What is more, a tran-
sition from reverse to direct micellar aggregates was ob-
served in this mixture. However, this idea was not sup-
ported with other data published in the literature (40, 58).
Nonaqueous liquid crystals: Lecithin is capable of
self-organizing into a liquid-crystalline state in such orga-
nic solvents as glycerol, ethylene glycol, and formamide
(40). The main feature of them is that they are prone to a
formation of numerous hydrogen bonds (75). When the
number of the H-bondings is decreased, as with forma-
mide derivatives prepared by a successive attachment of a
methyl group to the amino group, the liquid crystals cease
forming (76); e.g., lecithin in methylformamide is still
self-assembling into the liquid-crystalline state, though in
a shorter concentration range by comparison with its for-
mamide solutions, while these structures are not found
in dimethylformamide.
The formation of hydrogen bonds by the solvents, how-
ever, is the needed, but insufficient prerequisite (40).
Ethanol is an example. Lecithin self-assembles into mi-
cellar aggregates (Table 3), but its liquid crystals have not
been found in ethanolic solutions. Ethanol molecules are
linked to each other through hydrogen bonds arranged in
linear chains, whereas glycerol, ethylene glycol, and for-
mamide form three-dimensional networks from H-bon-
dings in the bulk (75). The same structural organization is
inherent in water. This provides a basis for hydrophobic
effects in water and solvophobic effects in the mentioned
organic solvents (42, 77). Surfactant molecules have a
tendency to minimize the contact area of their hydrocar-
bon chains with the solvent molecules. The lecithin self-
assembling into the liquid-crystalline state in glycerol,
ethylene glycol, and formamide is related in (40) to the
solvophobic effects.
As for the aqueous solutions, a predominant structure
for lecithin in glycerol, ethylene glycol, and formamide is
the La mesophase. Lecithin molecules are arranged in bi-
molecular layers of which the surface is covered with the
polar groups and the inner part is occupied by the hydro-
carbon chains. The solvent molecules create a solvation
shell around the functional groups of lecithin and fill in-
terlayers between bimolecular layers (76, 78). In a case of
ethylene glycol it was shown by means of a NMR spec-
troscopy that three types of solvent molecules could be
recognized by their mobility (78, 79). The same situation,
as considered in Lecithin-water section, was observed for
the hydration of lecithin in the La mesophase by the water
molecules.
It is common for molecules of the organic solvents in
the lamellar crystals not to penetrate into the region oc-
cupied by fatty acid residues. A special case is established
for benzene solutions. Lecithin self-assembles typically
into reversed micelles in benzene (Table 3). When con-
centrated solutions were cooled, a thickening was ob-
served (80). A detailed study revealed the presence of a
structure resembling the La mesophase (80, 81). Benzene
molecules are found in the regions of both the polar
groups of lecithin molecules and the hydrocarbon chains.
It should be pointed out that the capability of lecithin
to be self-organized into the lamellar structures is fun-
Table 3 Critical micelle concentrations for egg yolk lecithin in organic solutions
Solvent Aggregation number Concentration range (mM) Temperature (�C) Refs.
n-Heptane 5 > 0.01 25 66
Benzene 4– 6 < 0.1 25 12, 68, 70
73 > 1 25 68
55 40
15 15– 192 37 71
Toluene 82 3.7–15 25 72
65 40
Chloroform � 3 10– 130 1.5–44 73
Diethyl ether � 40 7– 10 25 74
Ethanol 9 3– 13 20 69
L
Lecithin 3003
damental importance for the living matter (82). The living
cycle of plants includes drying and cooling during the
winter season. This proceeds also with plant seeds, yeast
cells, fungal spores, and some microorganisms. The
drying and decreased temperature result in the transition,
as obvious from the phase diagram in Fig. 3, into a crys-
talline state. When the temperature has been increased
and water has been added, the disruption of the biological
membranes takes place. Therefore, it is a vital necessary
for the living systems to retain their intact structure after
the winter season. The retention of the La mesophase is
achieved by an exchange of water for polyols (glycerol
and ethylene glycol), disaccharides (trechalose and suc-
rose), or amino acids (proline) (83).
Ternary Systems
Ternary mixtures include normally water and oil. Lecithin
concentrates mainly at the interfacial boundaries, provid-
ing a stabilizing effect on various structures. Among them,
one can prepare swollen micelles, organogels, emulsions,
and liquid crystals. These systems are characterized below.
Swollen micelles
The micelle formation usually occurs in the organic media.
Therefore, the further consideration concerns reversed mi-
cellar aggregates.
Lecithin maintains its hygroscopy when it is dissolved
in nonaqueous solutions (40, 58). Water is absorbed from
the contacting air phase. From 15 up to 30 water mole-
cules per lecithin molecule can be attached to its polar
region as a hydration shell (70, 84, 85). It should be poin-
ted out that the initial spherical shape of micelles is not
changed in aromatic (benzene and toluene) and chlorina-
ted (chloroform and tetrachloride carbon) solvents (40, 58).
By dissolving water in the lecithin solution, one can ob-
tain swollen micelles. They consist of an inner water drop-
let (core) that is surrounded by a lecithin monolayer. Its
maximum diameters in benzene and tetrachloride carbon
solutions are 5.0 ± 1.5 and 3.0 ± 0.5 nm, respectively (84).
Organogel
The most common phenomenon for the nonaqueous le-
cithin solutions induced by dissolved water is a trans-
formation of the spherical micelles into cylindrical ag-
gregates (86, 87). Their molecular model is considered in
Nonaqueous systems section. The micellar shape change
takes place in more than 50 solvents including linear and
branched alkanes, cycloalkanes, ethers, and esters (86).
For example, in a case of n-decane or cyclohexane the
dissolution, respectively, of 2–3 or 7–10 water molecules
per lecithin molecule yields cylindrical aggregates of con-
tour length up to 1 mm, while the diameter is of about 5–7
nm (88, 89). Such the micelles entangle, making up a
temporal three-dimensional network in the bulk, much as
linear polymer molecules do it in semidilute solutions or
melts. This brings about a similar sharp increase in the
solution viscosity (90, 91). In place of the low viscous so-
lution, one will find a jelly-like phase (organogel). Owing
to similarity in the structural organization of the three-
dimensional network and the rheological behavior, these
lengthy cylindrical aggregates are known in the literature
as ‘‘polymer-like’’ micelles. They are also called ‘‘worm-
like’’ or ‘‘threadlike’’ micelles, ‘‘living’’ or ‘‘equilibrium’’
polymers.
The lecithin organogels are transparent, viscoelastic li-
quids. Their rheological behavior obeys a Maxwell model
(91, 92). This means that it can be presented in the form
of a dash-pot and spring connected in parallel. From the
structural point of view, the organogel is formed with a
three-dimensional network that is temporal, without fixed
contacts between entangled polymer-like micelles. The
dynamic behavior is described in the framework of a rep-
tation model (93). A polymer-like micelle moves like a
snake in an imaginary tubular-like space generated by
topological restrictions caused by neighboring micellar
aggregates.
It should be mentioned that the lecithin organogel exists
in a rather narrow range of water concentrations. In linear
alkanes, e.g., a homogeneous jelly-like phase is produced
when about 1.5 up to 3.0–3.5 water molecules per lecithin
molecule are added (94). If this amount has been
exceeded, there is a phase separation. At the initial stage
the water addition induces precipitation of a compact jelly-
like phase. With increasing amounts of water, a solid pre-
cipitate is formed. This is widely used in the manufacture
of vegetable oils for their refinement from PLs (see ‘‘No-
menclature, Structure, Sources, Composition, and Process-
ing’’). The process is known as degumming.
Emulsion
The emulsion is a dispersion of one immiscible liquid into
the other. From the thermodynamic point of view it is an
unstable system (67). The role of added surfactants goes
to slow down the kinetics of process (coalescence, floc-
culation, creaming, and Ostwald ripening) that lead to the
emulsion breakdown. Lecithin is believed to be an effec-
tive emulsifying agent (40, 95, 96). It normally brings
about the formation of water-in-oil emulsion because its
HLB (hydrophilic-lipophilic balance) value is of ca. 4
(34, 36). A rather stable emulsion is formed at the oil-to-
water ratio between 0.4 and 0.6 (97). The lecithin con-
centration should be higher than 0.5 wt%. The droplet
3004 Lecithin
diameter varies between 0.005 and 0.015 mm. Lecithin is
capable of stabilizing not only emulsions on the base of
aliphatic and aromatic hydrocarbons, but also fluorocar-
bon-based systems (98, 99); in this case a very stable oil-
in-water emulsion has been found (100) (see also Phar-
maceuticals and Diet Supplements section).
The increased stability of emulsion in the presence of
lecithin is often caused by the formation of a liquid-crys-
talline shell around the droplets (97, 101, 102). The shell
has a multilamellar structure that is caused by the pro-
pensity of lecithin for existing in the La mesophase (Leci-
thin-water section). This keeps effectively droplets from
coalescing, but the liquid crystalline shell cannot exclude
flocculation. Therefore, there is a necessity for additional
stabilization of the emulsion. This can be attained through
lecithin modification, addition of other PLs or surfactants
(see Formulations with phospholipids and surfactants
section for details).
Liquid-crystalline structures
Lecithin in binary mixtures with water exists predomi-
nantly as the lamellar phase La (Fig. 3). It can dissolve
some amounts of nonpolar solvents without a change its
phase state (40, 103, 104). When a critical concentration is
reached, there is a transition to a nonlamellar liquid crys-
talline form (cubic and reversed hexagonal HII phases;
their schematic drawings are shown in Fig. 3). In a case of
n-alkanes, it happens at about 8 wt% (103, 104). The
concentration, at which the phase transition is observed,
depends on the length of an alkane molecule, the fatty acid
residues in lecithin, the amount of water and the tempe-
rature. Higher alkane homologues tend to produce the
effect at larger concentrations (41, 47, 103). Their pene-
tration into the bimolecular layer and arrangement be-
tween hydrocarbon chains leads to an expansion of the non-
polar region, owing to an increased lateral pressure that
destabilizes the lamellar phase. A thermodynamic descrip-
tion of the phase transitions was developed by Gruner et al.
(105–107).
The addition of water into the nonaqueous lecithin
solutions does not include a direct transition into a liquid
crystalline state. The initial system consists of spherical
micelles. The polar additive brings about a change of other
micellar aggregates. In aromatic and chlorinated solvent
one can find swollen micelles. In the rest solvent there is a
transition into the jelly-like state at small water amounts
(Organogel section) and then a precipitation of solid
particles (94, 108). The formation of liquid crystalline
structures takes place at considerably larger water con-
centraions. A whole phase diagram for the lecithin-water-
cyclohexane system has been recently published by An-
gelico et al. (109). Ternary mixtures with other organic
solvent have been still only partially constructed (see, e.g.,
(110)).
Nonaqueus system
It was shown in the Lecithin-organic solvent section that
lecithin can self-organize into various structures in the
organic media or in the presence of organic solvents. This
propensity is retained in the ternary systems. It has not
been studied in sufficient details. One can find fragmen-
tary data in the literature.
Organogels: The addition of formamide, glycerol, or
ethylene glycol into a lecithin solution in alkanes makes
the initial nonviscous solution visoelastic (94, 108). This
phenomenon bears close similarity with that observed for
the water-containing organogels (see Organogel section).
The polar organic solvents induce also the uniaxial growth
of micelles that leads to a formation of polymer-like mi-
cellar aggregates. The micellar shape change is respon-
sible for the transition of nonviscous solution into the
jelly-like state. It was also shown (94, 108, 111) that the
mentioned organic solvents form hydrogen bonds with the
phosphate group in a lecithin molecule. For fairness sake,
it should be pointed out that experiments with polar orga-
nic additives provided a means for developing a molecular
model of polymer-like lecithin micelles. An approach used
was based on a comparison of various organic substances.
It was suggested (94, 112) that the stable polymer-like
aggregates are formed because of linear hydrogen bonding
networks composed of the phosphate groups of lecithin
and solvent molecules that serve as cross-linking (bridg-
ing) agents.
The lecithin organogels prepared by adding formamide,
glycerol, or ethylene glycol demonstrate rheological
behavior that is described in the framework of a Max-
well model (113). This means that the systems are made up
of a three-dimensional network of entangled entities mo-
ving in accordance with the reptation mechanism. It was
shown (113, 114) that the rheological properties of jelly-
like phases depend notably on the nature of the polar
additive. The organic solvents induce the formation of a
tighter network in comparison with water-containing sys-
tems. Furthermore, in their case the relaxation processes
are also faster that is the rearrangement of three-dimen-
sional micellar network formed by lecithin and polar or-
ganic solvents takes less time.
Nonaqueous microemulsion: A ternary microemul-
sion system with water is unknown. It has been found in
a case of ethylene glycol (115, 116). A microemulsion
exists at soybean lecithin concentration of 6–10 wt% in
case the diol content is varied in the range of 30–80 wt%.
After mixing all the components, droplets 100–150 nm in
diameter were formed. The nonaqueous system demons-
L
Lecithin 3005
trated limited stability. The authors observed a phase
separation with time.
Multicomponent Mixtures
Lecithin is widely used in numerous formulations, in-
cluding human and animal nutrition, medicine, cosmetics,
and a variety of industrial applications. They are normally
made up of more that three components. Because the for-
mulation are many and varied, it is impossible to list all of
them. Here will be considered only the main approaches
to the development of such practically important systems
as microemulsion and rules for mixing lecithin with PLs
and surfactants. At the end, lecithin-polymer complexes
are discussed.
Microemulsions
The microemulsion, as defined by Danielsson and Lindman
(117), is a homogeneous, optically isotropic and ther-
modynamically stable liquid solution. Because the diame-
ter of droplets of one liquid in another is usually in the
range of 1–10 nm (118), it is transparent or slightly opales-
cent. Lecithin is not, unfortunately, among the surfactants
that are able to stabilize microemulsion system alone. It
can be made, if a third solvent (co-solvent) or an additional
surfactant (co-surfactant) is additionally introduced.
Shinoda with collaborators were the pioneer investi-
gators who studied systematically a microemulsification
in oil-water mixtures in the presence of lecithin (119–
121). They found that a microemulsion was formed in a
soybean lecithin-water-hexadecane system with the addi-
tion of lower alcohols, ethanol, or propanol. The amount
of propanol was increased, as shown in Backlund and
Rantala (122), with changing hexadecane to dodecane,
The microemulsion formation was also observed in the
presence of triglycerides taken instead of alkane (123). It
was accompanied by a sharp decrease in the interfacial
tension (up to 4�10�4 mN/m at the oil/water interface
(124)). The microemulsification was strongly dependent
of the molecular weight of aliphatic alcohols. For in-
stance, a system with swollen micelles was found in place
of the microemulsion, once propanol was substituted
for butanol (119). On the other hack, n-butanol, sec-bu-
tanol, and iso-butanol were suited to form a microemul-
sion in the presence of isopropymyristate as the oil com-
ponent (125).
The useful recommendations for the preparation of le-
cithin-containing microemulsions have been developed by
Kahlweit et al. (126). They are the following. 1) When
lecithin is taken with shorter hydrocarbon chains, the
hydrophobicity (lipophilicity) of co-solvent or co-surfac-
tant should be increased; e.g., propanol can be substituted
for butanol. The needed effect in some instances can be
achieved by mixing of co-solvents (propanol with butanol
or butanol with pentanol). In this case, the hydropho-
bicity/hydrophilicity is changed in a delicate manner. 2)
The lower homologue of n-alkane, the less hydrophobic
co-solvent or co-surfactant should be taken. An example
is the following. By substituting hexadecane for hexane,
one should use ethanol in place of propanol. What is also
important, higher n-alkanes favor the microemulsification
of naturally occurring lecithins.
It was also suggested by Kahlweit et al. (127) to re-
place the aliphatic alcohols for less toxic 1,2-alkanediols.
Thus, propanol is successfully substituted for 1,2-pen-
tanediol in system containing soybean lecithin. This is in
agreement with observation made by Aboofazeli et al.
(128) who took isopropylmyristate was taken as the oil
phase. It was also shown that the lecithin microemulsions
could be prepared by addition of various co-surfactants
including fatty acids, polyethylene glycol alkyl ethers, or
alcohols. The effect of sugar-containing surfactants and
sodium taurocholate on the formation of lecithin micro-
emulsions were thoroughly studied by Voncorswant et al.
(129). The examined systems can be of interest for use in
cosmetics, pharmacology, etc. (130).
Formulations with phospholipids and surfactants
Lecithin is widely used in numerous formulations as the
emulsifier. Therefore, lots of studies are devoted to its
emulsifying properties. PLs and surfactants are the main
additives that are used to modify the emulsifying ability
of lecithin. Its stabilizing effect is often attributed to a
liquid-crystalline shell formed around the droplets (58, 97,
101, 102). This is enough to prevent them from the coa-
lescence, but processes such as flocculation and creaming
cannot be excluded. The effective way to do this is through
an introduction of PLs or surfactants. Their addition can
also lead to a change of the emulsion type. This has also
many uses.
If a formulation for food, cosmetic, or pharmacology is
developed, which are cases where it is desirable to hold
the lecithin biocompatibility, the best solution is to resort
to PLs. Their diversity provides various opportunities for
changing the stability and type of an emulsion.
The addition of PLs has various effects on the emul-
sifying ability of lecithin (40, 95–97, 131); e.g., phospha-
tidylethanolamine (Fig. 1), which is prone for the forma-
tion of reversed hexagonal phase (47, 48), enables one to
prepare a water-in-oil emulsion. The presence of lysoleci-
thin possessing only one hydrocarbon chain has an oppo-
site effect, i.e., a transition to an oil-in-water emulsion.
Anionic PLs, phosphatidic acid, phosphatidylserine, and
phosphatidylinositol (Fig. 1), provide a better stabilization
3006 Lecithin
of emulsions that neutral additives. Their effect is related
to the additional repulsive electrostatic forces. As shown
by Davis and Hansrani (132), the anionic PLs demonstra-
ted various efficacies. The most stability of oil droplets to
the coalescence in model experiments was observed for
mixtures of lecithin with phosphatidic acid. The least sta-
bilizing effect was found for phosphatidylinositol.
All the PLs mentioned above are widely used to im-
prove or change the lecithin functionality by mixing or
blending with it (19, 23, 34, 35, 133). Such mixtures or
blends are called compounded lecithins by manufacturers.
It should be pointed out that the crude lecithin is a mixture
of various PLs (see ‘‘Nomenclature, Structure, Sources,
Composition, and Processing’’). To modify its emulsify-
ing properties, it is subjected to fractionation and puri-
fication (22, 34) as well as modification through chemical
and enzymatic procedures (19–21, 34, 133). The manu-
facturers suggest numerous products including mixtures
with different lecithin content, with modified lecithins
and with various PLs.
Synthetic surfactants are also widely used as modified
additives to lecithin formulations or as agents providing
solubilization of PLs of the biological membranes. The
action of such surfactants as sodium dodecylsulfate, salts
of fatty acids, bile salts, cetyltrimethylammonium bro-