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The word gel is derived from gelatin, and both

gel and jelly can be traced back to the Latin gelu

for frost and gelare, meaning freeze or
congeal.

This origin indicates the essential idea of a liquid

setting to a solid-like material that does not flow, but

is elastic and retains some liquid characteristics.

The distinction between gel and jelly remains

somewhat arbitrary, with some differences based on

the field of application. The food industry uses the
term gelatin jelly whereas the pharmaceutical
industry uses the term gelatin gel.

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Gels are defined as semisolid systems consisting of

dispersions made up of either small inorganic particles or

large organic molecules enclosing and
interpenetrated by a liquid.

Some gel systems are as clear as water in appearance and

others are turbid, since the ingredients involved may not

be completely molecularly dispersed (soluble or insoluble)
or they may form aggregates, which disperse light.

The concentration of the gelling agents is mostly less than

10%, usually in 0.5 to 2.0% range, with some exceptions.

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Gels in which the macromolecules are

distributed throughout the liquid in such a

manner that no apparent boundaries exist
between them and the liquid are called singlephase gels. In instances in which the gel mass
consists of floccules of small distinct particles,
the gel is classified as a two-phase system and
frequently called a magma or a milk. Gels and
magmas are considered colloidal dispersions
since they each contain particles of colloidal
dimension.
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The majority of gels are formed by aggregation of

colloidal sol particles, the solid or semisolid system so

formed being interpenetrated by a liquid. The particles
link together to form an interlaced network, thereby
imparting rigidity to the structure; the continuous
phase is held within the meshes. Often only a small
percentage of disperse phase is required to impart
rigidity, for example 1 % of agar in water produces a
firm gel. A gel rich in liquid may be called a jelly; if the
liquid is removed and only the gel framework remains
this is termed a xerogel. Sheet gelatin, acacia tears
and tragacanth flakes are all xerogels.
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Many of the various types of colloidal dispersions have

been given appropriate names. For instance, sol is a

general term to designate a dispersion of a solid
substance in either a liquid, a solid, or a gaseous
dispersion medium.

However, more often than not it is used to describe the

solid-liquid dispersion system. To be more descriptive, a

prefix such as hydro- for water (hydrosol) or alco- for
alcohol (alcosol) may be employed to indicate the
dispersion medium.

The term aerosol has similarly been developed to indicate

a dispersion of a solid or a liquid in a gaseous phase.

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Certain terminology has been developed to

characterize the various degrees of attraction between

the phases of a colloidal dispersion. If the disperse
phase interacts appreciably with the dispersion
medium, it is referred to as being lyophilic, meaning
"solvent-loving. If the degree of attraction is small,
the colloid is termed lyophobic or "solvent-hating.

For instance, starch is lyophilic in water but lyophobic

in alcohol. Terms such as hydrophilic, and hydrophobic,

which are more descriptive of the nature of the
colloidal property, have therefore been developed to
refer to the attraction or lack of attraction of the
substance specifically to water.

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A third type of colloidal sol, termed as association or

amphiphilic colloid, is formed by the grouping or

association of molecules that exhibit both lyophilic and
lyophobic properties.

Lyophilic colloids are large organic molecules capable

of being solvated or associated with the molecules of

the dispersing phase. These substances disperse
readily upon addition to the dispersion medium to form
colloidal dispersions. As more molecules of the
substance are added to the sol, the viscosity is
characteristically increased and when the
concentration of molecules is sufficiently high, the
liquid sol may become a semisolid or solid dispersion,
termed a gel.

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 Some gels may be come fluid after agitation only to resume their

solid or semisolid state after remaining undisturbed for a period

of time, a phenomenon known as thixotrophy.

Lyophobic colloids are generally composed of inorganic particles.

When these are added to the dispersing phase, there is little if

any interaction between the two phases. Unlike lyophilic colloids,
lyophobic materials do not spontaneously disperse but must be
encouraged to do so by special, individualized procedures.

Their addition to the dispersion medium does not greatly affect

the viscosity of the vehicle.

Some substances such as acacia are termed natural colloids

because they are self-dispersing upon addition to the dispersing

medium.

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Terminology Related to
Gels
A number of terms are commonly used in discussing
some of the characteristics of gels, including
imbibition, swelling, syneresis, thixotropy and xerogel.

Imbibition is the taking up of a certain amount of

liquid without a measurable increase in volume.

Swelling is the taking up of a liquid by a gel with an

increase in volume. Only those liquids that solvate a

gel can cause swelling. The swelling of protein gels
is influenced by pH and the presence of electrolytes.

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10

Syneresis is when the interaction between particles

of the dispersed phase becomes so great that on

standing, the dispersing medium is squeezed out in
droplets and the gel shrinks. Syneresis is a form of
instability in aqueous and non-aqueous gels.

Thixotropy is a reversible gel-sol formation with no

change in volume or temperature. A type of nonNewtonian flow.

A xerogel is formed when the liquid is removed

from a gel and only the framework remains.

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11

Gelation of lyophobic sols

Gels may be

flocculated lyophobic
sols where the gel
can be looked upon
as a continuous
floccule.
Examples are:
aluminium hydroxide
and magnesium
hydroxide gels.

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Gel structure,
Flocculated lyophobic
sol, e.g. aluminium
hydroxide.
12

Clays such as bentonite, aluminium magnesium

silicate (Veegum) and to some extent kaolin

form gels by flocculation in a special manner.
They are hydrated aluminium (aluminium /
magnesium) silicates whose crystal structure is
such that they exist as flat plates; the flat part
or 'face' of the particle carries a negative
charge due to O atoms and the edge of the
plate carries a positive charge due to Al 3+/Mg2+
atoms.
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13

As a result of
electrostatic
attraction between
the face and the
edge of different
particles a gel
structure is built up,
forming what is
usually known as a
'card house floc'.
Gel structure, 'Card house' floc of clays, e.g.
bentonite.

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14

The forces holding the particles together in this

type of gel are relatively weak - van der Waals

forces in the secondary minimum flocculation of
aluminium hydroxide, electrostatic attraction in
the case of the clays - and because of this these
gels show the phenomenon of thixotropy, a nonchemical isothermal gel-sol-gel transformation.
If a thixotropic gel is sheared (for example by
simple shaking) these weak bonds are broken and
a lyophobic sol is formed. On standing the
particles collide, flocculation occurs and the gel is
reformed.
Flocculation in gels is the reason for their
anomalous rheological properties.
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15

Gelation of lyophilic sols

Gels formed by lyophilic sols can be divided into

two groups depending on the nature of the bonds

between the chains of the network.
Gels of type I are irreversible systems with a threedimensional network formed by covalent bonds
between the macromolecules. Typical examples are
the swollen networks that have been formed by the
polymerization of monomers of water-soluble
polymers in the presence of a crosslinking agent.
For example, poly (2-hydroxyethylmethacrylate),
[poly (HEMA)], crosslinked with ethylene glycol
dimethacrylate, [EGDMA], forms a threedimensional structure, that swells in water but
cannot dissolve because the crosslinks are stable.
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16

Such polymers have been used in the

fabrication of expanding implants that imbide

body fluids and swell to a predetermined
volume.
Implanted in the dehydrated state these
polymers swell to fill a body cavity or give
form to surrounding tissues.

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17

Poly (HEMA):poly (2-hydroxyethyl methacrylate)

cross-linked with ethylene glycol dimethacrylate

(EGDMA)
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18

Type II gels are held together by much weaker

intermolecular bonds such as hydrogen bonds. These

gels are heat reversible, a transition from the sol to gel
occurring on either heating or cooling.

Poly (vinyl alcohol) solutions, for example, gel on cooling

below a certain temperature referred to as the gel point.

Because of their gelling properties poly (vinyl alcohol)s

are used as jellies for the application of drugs to the

skin. On application the gel dries rapidly, leaving a
plastic film with the drug in intimate contact with the
skin.
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19

 Concentrated aqueous solutions of high molecular weight

poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)
block copolymers, form gels on heating.

These compounds are amphiphilic, and many form

micelles with a hydrophobic core comprising the

poly(oxypropylene) blocks surrounded by a shell of the
hydrophilic poly(oxyethylene) chains. Unusually, water is
a poorer solvent for these compounds at higher
temperatures and consequently warming a solution with
a concentration above the critical micelle concentration
leads to the formation of more micelles. If the solution is
sufficiently concentrated gelation may occur as the
micelles pack so closely as to prevent their movement.
Gelation is a reversible process, the gels returning to the
sol state on cooling.
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20

Amphiphiles, surface-active agents, or

surfactants in Gels
Certain compounds, because of
their chemical structure, have a
tendency to accumulate at the
boundary between two phases.
Such compounds are termed

amphiphiles, surface-active agents,

or surfactants.
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21

Poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block
copolymers.
(a) Micelle formation, (b) Formation of a cubic gel phase by
packing of micelles.
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22

Classification of Gels
Gels may be classified into two primary types:

hydrogels, which have an aqueous continuous

phase, and organogels, which have an organic
solvent as the liquid continuous medium.
Gels may also be classified based on the nature
of the bonds involved in the three dimensional
solid network: chemical gels form when strong
covalent bonds hold the network together, and
physical gels form when hydrogen bonds and
electrostatic and van der Waals interactions
maintain the gel network.
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23

Gelling agents
Gelling agents commonly used are synthetic macromolecules

(e.g., carbomer 934), cellulose derivatives (e.g.,

carboxymethylcellulose and hydroxypropylmethylcellulose),
and natural gums (e.g., tragacanth).

Carbomers in particular are high molecular- weight water-

soluble polymers of acrylic acid cross-linked with allyl ethers

of sucrose and/or pentaerythritol.

The NF contains monographs for six such polymers:

carbomers 910, 934, 934P, 940, 941, and 1342. They are
used as gelling agents at concentrations of 0.52.0% in water.
Carbomer 940 yields the highest viscosity: between 40,000
and 60,000 CP as a 0.5% aqueous dispersion. Depending on
their polymeric composition, different viscosities result.

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24

The USP defines gels (sometimes called jellies) as

semisolid systems consisting of either suspensions

made up of small inorganic particles, or large
organic molecules interpenetrated by a liquid.
Where the gel mass consists of a network of small
discrete particles, the gel is classified as a twophase system.

Single-phase gels consist of organic macromolecules

uniformly distributed throughout a liquid in such a

manner that no apparent boundaries exist between
the dispersed macromolecules and the liquid.
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25

 A gel mass consisting of floccules of small distinct particles is termed

a two-phase system, often referred to as a magma.

Gels may thicken on standing, forming a thixotrope, and must be

shaken before use to liquefy the gel and enable pouring.

In addition to the gelling agent and water, gels may be formulated to

contain a drug substance, solvents, such as alcohol and/or propylene

glycol; antimicrobial preservatives, such as methylparaben and
propylparaben or chlorhexidine gloconate; and stabilizers, such as
edetate disodium.
Medicated gels may be prepared for administration by various routes,

including the skin, the eye, the nose, the vagina, and the rectum.

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26

PHYSICAL PROPERTIES OF GELS

AND JELLIES
The physical properties of gels and jellies can

be classified into two groups: transitional

properties (including gel point, retrogradation,
and syneresis) and rheological properties
(including rigidity, yield point, and rupture
strength). The experimental techniques used
to characterize these physical properties can
be similarly classified.

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27

Mechanical techniques are used to determine

rheological properties of gels. These

techniques employ either small-deformation
measurements that yield viscoelastic
parameters or large-deformation
measurements that generate complete stressstrain profiles, which include failure
parameters.

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28

Gelling concentrations for substances used in

pharmaceutical products:
Substance
GelRequired
forming
additives
concentrati
ons (wt %)
Proteins
- Collagen
- Gelatin
Polysaccharides
- Agar
- Alginates
- Pectins
methyoxy)

0.20.4a
215
0.11
0.51
510
(low 0.82

Ca+2
Na+
Ca+2

Adjusted to pH > 4 and warmed to 37 C.

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29

Substance

Gelforming
concentrat
ions (wt
%)

Semisynthetic polymers
(cellulose derivatives)
- Carboxymethylcellulose

46
1025
- Hydroxypropylcellulose 8-10
- 2-10
Hydroxypropylmethylcellulo
se
- Methylcellulose
24
03/29/16

Requir
ed
additiv
es

Na+
Na+

30

Substance

Synthetic
polymers
- Carbomer
- Poloxamer
Polyacrylamide
- Polyvinyl
alcohol

Gel-forming Required
concentratio additives
ns (wt %)
0.52
1550
4
1020

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31

Substance

Inorganic substances
- Aluminum
hydroxide
- Bentonite
Surfactants
- Cetostearyl alcohol
- Brij 96b
b

Gel-forming Required
concentrati additives
ons (wt %)
35
5
10
4060

Cetrimide

Brij 3099 surfactants are polyoxyethylene-alkyl ethers.

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32

Clearly, gels are semisolids that have both solid

and liquid character under stressthey are

viscoelastic substances.

Gel-forming hydrophilic polymers are typically

used to prepare lipid-free semisolid dosage forms,

including dental, dermatological, nasal,
ophthalmic, rectal, and vaginal gels and jellies. Gel
vehicles containing therapeutic agents are
especially useful for application to mucous
membranes and ulcerated or burned tissues
because their high water content reduces irritancy.

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33

Furthermore, these hydrophilic gels are easily

removed by gentle rinsing or natural flushing

with body fluids, reducing the propensity for
mechanical abrasion. The superior optical
clarity of synthetic polymer gels, such as
those composed of poloxamer and carbomer,
has led to the interest in developing
therapeutic ophthalmic gels.

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34

In addition to serving as drug-containing

vehicles, some gels have other important

functions. For example, a soft, flexible gel
applied to burned skin can prevent excessive
water loss by forming a physical barrier.
Ocular gel inserts are designed to lubricate
the eye continuously and promote healing.
Still other gels are intended for lubricating
surgical and medical instruments in order to
minimize local irritation.
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35

Many gel-forming substances are available for

preparing pharmaceutical gels and jellies. Although

these substances share some common physical
characteristics, the intended use may require gelling
attributes of a certain substance or blend of
substances.

For example, Pharmaceutical Nasal Gels must be:

1. Nasal adherent
2. Odorless
3. Non-irritating
4. Water soluble
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36

And Pharmaceutical Ophthalmic Gels must be:

1. Optically clear
2. Sterile
3. Mucomimetic
4. Lubricating
5. Demulcent
6. Non-irritating or non-sensitizing
7. Water soluble or miscible
Some simple gel formulations are shown as

following:

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37

Carbomer 941 gel

Carbomer 941
0.5 (% w/w)
Glycerine
10.0 (% w/w)
Triethanolamine
0.5 (% w/w)
Water
89.0 (% w/w)
Preservative q.s.

Procedure: Water, glycerine, and preservative are

mixed and the carbomer added by sprinkling on
the surface while constantly mixing at high
speed. Triethanolamine is added with slow
agitation until a clear viscous gel forms.
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38

Carbomer 934 alcoholic

gel
Carbomer 934 resin
3.0 (% w/w)
Glycerine
10.0 (% w/w)
Ethanol 40.0 (% w/w)
2-Ethylhexylamine 2.5 (% w/w)
Water
44.5 (% w/w)

Procedure: The carbomer is dispersed in the

glycerine and water, and a solution of the 2ethylhexylamine in ethanol is added to the water
solution with mixing until a clear transparent gel
is formed.
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39

Practical Example on
Medicated Gels:
Benzocaine Gel
Benzocaine is a local anesthetic commonly

used as a topical pain reliever. It is the active

ingredient in many over-the-counter
anesthetic ointments. It is also combined with
antipyrine to form Anti-Biotic Otic Drops, to
relieve ear pain and remove earwax.
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40

Benzocaine is used as a key

ingredient in numerous
An anti-inflammatory.
pharmaceuticals:
Over the counter throat lozenges.
Some glycerol-based ear medications for use in

removing excess wax as well as relieving ear

conditions such as Otitis Media and swimmers ear.
Some previous diet products.
Some condoms designed to prevent premature
ejaculation. Benzocaine acts to desensitize the
penis, and theoretically allows an erection to be
maintained.
Treating pain from mouth and gum irritations (eg,
canker sores).
03/29/16

41

Before using
Benzocaine
Some medical conditions mayGel:
interact with Benzocaine
Gel. Tell your doctor or pharmacist if you have any
medical conditions, especially if any of the following
apply to you:
if you are pregnant, planning to become pregnant, or
are breast-feeding.
if you are taking any prescription or nonprescription
medicine, herbal preparation, or dietary supplement.
if you have allergies to medicines, foods, or other
substances.

Because little, if any, of Benzocaine Gel is absorbed into

the blood, the risk of it interacting with another
medicine is low.
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42