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
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.
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 single-phase 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.
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.
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
The term aerosol has similarly been developed to indicate a
dispersion of a solid or a liquid in a gaseous phase.
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
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
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
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.
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.
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 xero-gel.
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.
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
Thixotropy is a reversible gel-sol formation with no change
in volume or temperature. A type of non-Newtonian flow.
A xerogel is formed when the liquid is removed from a gel
and only the framework remains.
Gelation of lyophobic sols
Gels may be flocculated
lyophobic sols where the
gel can be looked upon
as a continuous floccule.
Gel structure, Flocculated
lyophobic sol, e.g.
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
As a result of
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.
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 non-chemical isothermal gel-sol-gel
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
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 three-
dimensional 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
For example, poly (2-hydroxyethylmethacrylate), [poly
(HEMA)], crosslinked with ethylene glycol dimethacrylate,
[EGDMA], forms a three-dimensional structure, that swells
in water but cannot dissolve because the crosslinks are
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
Poly (HEMA):poly (2-hydroxyethyl methacrylate) cross-
linked with ethylene glycol dimethacrylate (EGDMA)
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.
Concentrated aqueous solutions of high molecular weight
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.
Amphiphiles, surface-active agents, or surfactants
Certain compounds, because of their
chemical structure, have a tendency to
accumulate at the boundary between two
Such compounds are termed
amphiphiles, surface-active agents, or
(a) Micelle formation, (b) Formation of a cubic gel phase by packing of
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.
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 0.5–2.0% 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.
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 two-phase 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.
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.
PHYSICAL PROPERTIES OF GELS AND
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.
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 stress-strain
profiles, which include failure parameters.
Gelling concentrations for substances used in pharmaceutical
Substance Gel-forming Required
ns (wt %)
- Collagen 0.2–0.4a
- Gelatin 2–15
- Agar 0.1–1
- Alginates 0.5–1 Ca+2
- Pectins (low methyoxy) 0.8–2 Ca+2
aAdjusted to pH > 4 and warmed to 37 °C.
Substance Gel-forming Require
ns (wt %) additive
- Carboxymethylcellulose 4–6 Na+
- Hydroxypropylcellulose 8-10
- Methylcellulose 2–4
Substance Gel-forming Required
- Carbomer 0.5–2
- Poloxamer 15–50
- Polyacrylamide 4
- Polyvinyl alcohol 10–20
Substance Gel-forming Required
s (wt %)
- Aluminum hydroxide 3–5
- Bentonite 5
- Cetostearyl alcohol 10 Cetrimide
- Brij 96b 40–60
bBrij 30–99 surfactants are polyoxyethylene-alkyl ethers.
Clearly, gels are semisolids that have both solid and
liquid character under stress—they are viscoelastic
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.
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
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.
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
4. Water soluble
And Pharmaceutical Ophthalmic Gels must be:
1. Optically clear
6. Non-irritating or non-sensitizing
7. Water soluble or miscible
Some simple gel formulations are shown as following:
Carbomer 941 gel
Carbomer 941 0.5 (% w/w)
Glycerine 10.0 (% w/w)
Triethanolamine 0.5 (% w/w)
Water 89.0 (% w/w)
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.
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 2-ethylhexylamine in ethanol
is added to the water solution with mixing until a clear
transparent gel is formed.
Practical Example on Medicated
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.
Benzocaine is used as a key ingredient
in numerous 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
Before using Benzocaine Gel:
Some medical conditions may 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
if you are taking any prescription or nonprescription
medicine, herbal preparation, or dietary supplement.
if you have allergies to medicines, foods, or other
Because little, if any, of Benzocaine Gel is absorbed into the
blood, the risk of it interacting with another medicine is