Are View On Pharmaceutical Gel

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A Review on Pharmaceutical Gel
Article in International Journal of Pharmaceutical Sciences · October 2015
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Acta Scientifica International Journal of Pharmaceutical Science
Volume 1 Issue 1 September 2015
Review Article

Hemendrasinh J Rathod1* and Dhruti P Mehta2
1
Department of Pharmaceutics, Vidyabharti Trust College of Pharmacy, India
2
Department of Pharmaceutics, Vidyabharti Trust College of Pharmacy, India
*Corresponding Author: Hemendrasinh J Rathod, Vidyabharti Trust College of Pharmacy, Umrakh - 394 345, Gujarat, India.
Received: July 27, 2015; Published: September 30, 2015
Abstract
The purpose of writing this review was to compile the recent literature with a special focus on a rational approach to topical formu-
lation and basic components of topical drug delivery systems. Topical applications of drugs have advantages of delivering the drug
directly to the site of action and acting for a longer period of time. Skin is one of the most widespread and readily accessible organs on
the human body for topical administration and is the main route of topical drug delivery system. Many widely used topical agents like
ointments, creams and lotions have numerous disadvantages as they are usually very sticky causing uneasiness to the patient when
applied. Moreover, they also have less spreading coefficient and need to apply with rubbing and also exhibit the problem of stabil-
ity, due to all these factors, within the major group of semisolid preparations; the use of gas has increased both in cosmetics and in
pharmaceutical preparations. A gel is colloid that is typically 99% by weight liquid, which is immobilized by surface tension between
it and a macromolecular network of fibers built from a small amount of a gelatinous substance present.
Keywords: Pharmaceutical gels; Terminologies; Characteristics; Classification; Preparation; Evaluation of Gels; Patents
Introduction
Gels are defined as semi rigid systems in which the movement of the dispersing medium is restricted by an interlacing three-dimen-
sional network of particles or solvated macromolecules of the dispersed phase.
The word ‘‘gel’’ is derived from ‘‘gelatin,’’ and both ‘‘gel’’ and ‘‘jelly’’ can be drawn back to the Latin gelu for ‘‘frost’’ and gel are, mean-
ing ‘‘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. Use of the term ‘‘gel’’ as a classification originated during the late 1800s as chemists attempted to
classify semisolid substances according to their phenomenological characteristics rather than their molecular compositions. At that time,
analytical methods needed to determine chemical structures were lacking.
The USP defines gels (sometimes called jellies) as semisolid systems containing either suspensions made up of small inorganic par-
ticles, or large organic molecules interpenetrated by a liquid. Where the gel mass contains a network of small separate particles, the gel
is classified as a two-phase system. In a two-phase system, if the particle size of the dispersed phase is relatively large, the gel mass is
sometimes called as a magma. Single-phase gels consist of organic macromolecules uniformly circulated throughout a liquid in such a way
that no apparent boundaries occur between the dispersed macromolecules and the liquid.
In pharmaceutical applications, water and hydroalcoholic solutions are most common. Many polymer gels exhibit reversibility be-
tween the gel state and sol, which is the fluid phase containing the dispersed or dissolved macromolecule. However, the formation of some
polymer gels is irreversible because their chains are covalently bonded. The three-dimensional networks formed in two-phase gels and
jellies are formed by several inorganic colloidal clays. The formation of these inorganic gels is reversible.
Citation: Hemendrasinh J Rathod and Dhruti P Mehta. “A Review on Pharmaceutical Gel”. International Journal of Pharmaceutical Sciences 1.1 (2015):
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Gels are generally considered to be more rigid than jellies because gels contain more covalent crosslinks, a higher density of physical
bonds, or simply less liquid. Gel-forming polymers produce materials that span a range of rigidities, beginning with a sol and increasing
in rigidity to a mucilage, jelly, gel, and hydrogel.
Some gel systems are as clear as water, and others are turbid because the ingredients 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.
Terminologies Related to Gels [1]

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 taking up of a liquid by a gel with a rise in the volume. Only liquids that solvate a gel can cause swelling. The swelling of pro-
tein gels is influenced by pH and the presence of electrolytes.
Syneresis happens when the interaction between particles of the dispersed phase becomes so great that on standing, the dispersing
medium is pressed out in droplets and the gel shrinks. It is a form of unpredictability in aqueous and non-aqueous gels. Separation of a
solvent phase is thought to occur because of the elastic contraction of the polymeric molecules; in the swelling process during gel forma-
tion the macromolecules become stretched, and the elastic forces increase as swelling proceeds. At equilibrium the restoring force of the
macromolecules is balanced by the swelling forces, determined by the osmotic pressure. If the osmotic pressure decreases, as on cooling,
water may be squeezed out of the gel. The syneresis of an acidic gel from Plantago albicans seed gum may be decreased by the addition
of electrolyte, glucose, and sucrose and by increasing the gum concentration. pH has a marked effect on the separation of water. At low
pH marked syneresis occurs, possibly as a result of suppression of ionization of the carboxylic acid groups, loss of hydrating water, and
the formation of intramolecular hydrogen bonds. This would reduce the attraction of the solvent for the macromolecule.
Thixotropy is a reversible gel-sol formation with no change in volume or temperature, a type of non-Newtonian flow.
Xerogel is formed when the liquid is removed from a gel and only the framework remains.
E.g., Gelatin sheets, tragacanth ribbons, acacia tears, etc.
Structure of Gels [4]

The rigidity of a gel arises from the presence of a network formed by the interlinking of particles gelling agent. The nature of the
particles and the type of force that is responsible for the linkages, which determines the structure of the network and the properties of
the gel.
The individual particles of the hydrophilic colloid may consist of either spherical or an isometric aggregate of small molecules, or
single macromolecules. Possible arrangements of such particles in a gel network are shown in (Figure 1) [5]. In linear macromolecules
the network is comprised of entangled molecules, the point of contact between which may either be relatively small or consist of several
molecules aligned in a crystalline order, as shown in Figure 1 (c) and (d), respectively.
The forces of attraction responsible for the linkage between gelling agent particles may range from strong primary valencies, as in
silicic acid gels, to weaker hydrogen bonds and Vander Waals forces. The weaker nature of these latter forces is indicated by the fact that
a slight increase in temperature often causes liquefaction of gel.
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Figure 1: Representations of gel structures. (a) Flocculated particles in a two-phase gel structure.
(b) Network of elongated particles or rods forming a gel structure. (c) Matted fibers as found in
soap gels. (d) Crystalline and amorphous regions in a gel of carboxymethylcellulose.
Properties of Gels [1,2,4,6]

1. Ideally, the gelling agent must be inert, safe and cannot react with other formulation constituents.
2. The gelling agent should produce a sensible solid-like nature at the time of storage which is easily broken when exposed to shear
forces produced by squeezing the tube, trembling the bottle or at the time of topical application.
3. It should have suitable anti-microbial agent.
4. The topical gel must not be sticky.
5. The ophthalmic gel must be sterile.
6. The apparent viscosity or gel strength increases with an increase in the effective crosslink density of the gel. However, a rise in
temperature may increase or decrease the apparent viscosity, depending on the molecular interactions between the polymer and
solvent.
7. They exhibit the mechanical characteristics of the solid state.
8. Each component is continuous throughout the system.
9. There is high degree of attraction amongst the dispersed phase and water medium so the gels remain equally uniform upon stand-
ing and doesn’t freely settle.
Characteristics of Gels [4,7]
Swelling
Gels can swell, absorbing liquid with an increase in volume. This can be looked on as the initial phase of dissolution. Solvent pen-
etrates the gel matrix so that gel-gel interactions are replaced by gel-solvent interactions. Limited swelling is usually the result of some
degree of cross-linking in the gel matrix that prevents total dissolution. Such gel swells considerably when the solvent mixture possesses
a solubility parameter comparable to that of the gellant.
Syneresis
Many gel systems undergo contraction upon standing. The interstitial liquid is expressed, collecting at the surface of the gel. This
process, referred to as syneresis, is not limited to organic hydrogels, but has been seen in organogels and inorganic hydrogels as well.
Typically, syneresis becomes more pronounced as the concentration of polymer decreases.
The mechanism of contraction has been related to the relaxation of elastic stresses developed during the setting of the gel. As these
stresses are relieved, the interstitial space available for solvent is reduced, forcing the expression of fluid. Osmotic effects have been
implicated, as both pH and electrolyte concentration influence syneresis from gels composed of the ionic gel formers gelatin or psyllium
seed gum.
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Ageing
Colloidal systems usually exhibit slow spontaneous aggregation. This process is referred to as ageing. In gels, ageing results in the
gradual formation of a dense network of the gelling agent. The imer suggests that this process is similar to the original gelling process
and continues after the initial gelation, since the fluid medium is lost from the newly formed gel.
Structure
The rigidity of a gel arises from the presence of a network formed by the interlinking of particles of the gelling agents. The nature
of the particle and the type of force that is responsible for the linkages determine the structure of the network and the properties of the
gel.
Rheology
Solutions of the gelling agents and dispersion of flocculated solid are pseudo plastic i.e., exhibiting Non-Newtonian flow behavior,
characterized by a decrease in viscosity with an increase in shear rate. The tenuous structure of inorganic particles dispersed in water is
disrupted by applied shear stress due to breaking down of interparticulate association, exhibiting a greater tendency to flow. Similarly,
for macromolecules the applied shear stress aligns the molecules in the direction of stress, straightening them out and lessening the
resistance to flow.
Uses of Gels [7]

1. As delivery systems for orally administered drugs.
2. For topical drugs applied directly to the skin, mucous membrane or the eye.
3. As long acting forms of drug injected intramuscularly or implanted into the body.
4. As binders in tablet granulation, protective colloids in suspensions, thickeners in oral liquid and suppository bases.
5. In cosmetics like shampoos, fragrance products, dentifrices and skin and hair care preparations.
6. Lubricant for catheters
7. Bases for patch testing
8. NaCl gel for electrocardiography
9. Sodium fluoride & Phosphoric acid gel for dental care prophylactic
Classification of Gels [1,6,8]

Gels can be classified based on colloidal phases, nature of solvent used, physical nature and rheological properties, etc.
Based on colloidal phases

They are classified into:
a. Inorganic (Two phase system)
b. Organic (Single phase system)
Inorganic (Two phase system)

If the partition size of dispersed phase is relatively large and form the three-dimensional structure throughout gel, such a system
consists of floccules of small particles rather than larger molecules and gel structure, in this, system is not always stable. They must be
thixotropic-forming semisolid on standing and become liquid on agitation.
Organic (Single phase system)

These consist of large organic molecules existing on the twisted strands dissolved in a continuous phase. This larger organic mol-
ecule either natural or synthetic polymers are referred as gel formers, they tend to entangle with each other their random motion or
bound together by Vander walls forces.
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Based on nature of solvent
Hydrogels (Water based)

A hydrogel is a network of polymer chains that are hydrophilic, infrequently found as a colloidal gel in which water is dispersion
medium. They are highly absorbent natural or synthetic polymeric networks. They also have a degree of flexibility likely to the natural
tissue, due to their significant water content.
Uses for hydrogels
1. Sustained-release drug delivery systems

2. Rectal drug delivery and diagnosis
3. Hydrogel-coated wells have been used for cell culture
4. As scaffolds in tissue engineering
5. As environment sensitivity detector
6. Contact lenses (silicone hydrogels, polyacrylamides, polymacon)
7. ECG medical electrode
8. Dressing of healing
E.g., Bentonite magma, gelatin, cellulose derivatives, carpooler and poloxamer gel.
Organogels (With a non-aqueous solvent)

An organogel is a non-crystalline, non-glassy thermoreversible solid material composed of a liquid organic phase trapped in a 3D
cross-linked network. The liquid can be, E.g., vegetable oil, an organic solvent or mineral oil. The solubility and particle sizes of the
structurant are significant characteristics for the elastic properties and firmness of the organogel. Frequently, these systems are based
on self-assembly of the structurant molecules.
Xerogels
It is a solid formed from a gel by drying with unrestricted shrinkage. It is frequently retains high porosity (15-50%) and huge sur-
face area (150-900 m2/g), along with very small pore size (1-10 nm). When solvent removed under supercritical conditions, the net-
work doesn’t shrink and a highly porous, low-density material known as an aerogel is produced. Heat treatment of a xerogel at higher
temperature produces viscous sintering and efficiently transforms the porous gel into a thick glass.
E.g., Tragacanth ribbons, β-cyclodextrin, dry cellulose and polystyrene, gelatin sheets and acacia tears.
Based on rheological properties

Usually gels exhibit non-Newtonian flow properties. They are classified into:
a. Plastic gels
b. Pseudo plastic gels
c. Thixotropic gels
Plastic gels
E.g., Bingham bodies, flocculated suspensions of Aluminum hydroxide exhibit a plastic flow and the plot of rheogram gives the yield
value of the gels above which the elastic gel distorts and begins to flow.
Pseudo-plastic gels
E.g., Liquid dispersion of tragacanth, sodium alginate, Na CMC, etc. exhibits pseudo-plastic flow. The viscosity of these gels de-
creases with increasing rate of shear, with no yield value. The rheogram results from a shearing action on the long chain molecules of
the linear polymers. As the shearing stress is increased the disarranged molecules begin to align their long axis in the direction of flow
with the release of solvent from gel matrix.
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Thixotropic gels
The bonds between particles in these gels are very weak and can be broken down by shaking. The resulting solution will revert back
to gel due to the particles colliding and linking together again (the reversible isothermal gel-sol-gel transformation). This occurs in a
colloidal system with non-spherical particles to build up a scaffold like structure.
E.g., Kaolin, bentonite, agar, etc.
Based on physical nature
Elastic gels
Gels of agar, pectin, Guar gum and alginates exhibit an elastic behavior. The fibrous molecules being linked at the point of junction by
comparatively weak bonds like hydrogen bonds and dipole attraction. If the molecule possesses free -COOH group then additional
bonding takes place by a salt bridge of type -COO-X-COO between two adjacent strand networks.
E.g., Alginate and Carbopol.
Rigid gels
This can be formed from macromolecule in which the framework linked by primary valence bonds.
E.g., In silica gel, silic acid molecules are held by Si-O-Si-O bond to give a polymer structure possessing a network of pores.
Preparation of Gels [8]

Gels are normally in the industrial scale prepared under room temperature. However, few of polymers need special treatment be-
fore processing. Gels can be prepared by following methods:
1. Thermal changes
2. Flocculation
3. Chemical reaction
Thermal changes
Solvated polymers (lipophilic colloids) when subjected to thermal changes causes gelatin. Many hydrogen formers are more sol-
uble in hot than cold water. If the temperature is reduced, the degree of hydration is decreased and gelation takes place. (Cooling of a
concentrated hot solution will produce a gel).
E.g., Gelatin, agar sodium oleate, guar gummed, cellulose derivatives, etc. In contrast to this, some materials like cellulose ether
have their water solubility to hydrogen bonding with the water. Raising the temperature of these solutions will disrupt the hydrogen
bonding and reduced solubility, which will cause gelation. Hence this method cannot be adopted to prepare gels as a general method.
Flocculation
Here gelation is produced by adding just sufficient quantity of salt to precipitate to produce age state, but inadequate to bring about
complete precipitation. It is essential to ensure quick mixing to avoid local high concentration of precipitant.
E.g., Solution of ethyl cellulose, polystyrene in benzene can be gelled by quick mixing with suitable amounts of a non-solvent such
as petroleum ether. The adding of salts to hydrophobic solution brings about coagulation, gelation is infrequently observed. The gels
formed by flocculation method are Thixotropic in behavior. Hydrophilic colloids such as gelatin, proteins and acacia are only affected
by high concentration of electrolytes, when the effect is to “salt out”, the colloidal and gelation doesn’t occur.
Chemical reaction
In this method gel is produced by chemical interaction between the solute and solvent.
E.g., Aluminium hydroxide gel can be prepared by interaction in aqueous solution of an aluminium salt and sodium carbonate an
increased concentration of reactants will produce a gel structure. Few other examples that involve chemical reaction between PVA,
cyanoacrylates with glycidol ether (Glycidol), toluene diisocyanates (TDI), methane diphenyl isocyanine (MDI) that cross-links the
polymeric chain.
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Substance Gel-forming Required additives

concentrations (wt%)
Proteins
Collagen 0.2-0.4a
Gelatin 2-15
Polysaccharides
Agar 0.1-1
Alginates 0.5-1 Ca2+
5-10 Na+
K-Carrageenan 1-2 K+
Gellum gum (low acetyl) 0.5-1 Ca2+
Glycyrrhiza 2
Guar gum 2.5–10
0.25 Borate ion
Hyaluronic acid 2
Pectins (low methyoxy) 0.8-2 Ca2+
Starch 6
Tragacanth gum 2-5
Semisynthetic polymers
(cellulose derivatives)
Carboxymethylcellulose 4-6 Na+
10-25 Na+
Hydroxypropylcellulose 8-10
Hydroxypropylmethylcellulose 2-10
Methylcellulose 2-4
Synthetic polymers
Carbomer 0.5-2
Poloxamer 15-50
Poyacrylamide 4
Polyvinyl alcohol 10-20
Inorganic substances
Aluminum hydroxide 3-5
Bentonite 5
Laponite 2 Electrolytes
Surfactants
Cetostearyl alcohol 10 Cetrimide
Brij 96b 40-60
Table 1: Gelling Concentrations for Substances Used In Pharmaceutical Products [2].

a
Adjusted to pH > 4 and warmed to 37ºC.
b
Brij 30-99 surfactants are polyoxyethylene-alkyl ethers.
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Applications Favorable Applications Favorable properties

properties
Dental Highly thixotropic Ophthalmic Optically clear
Optimal viscosity for filling Sterile
fissures
Adherent to enamel sur- Non-irritating or
faces non-sensitizing
Optically clear Mucomimetic
Water soluble Demulcent
Orally digestible Lubricating
Dermatological Thixotropic Water soluble or miscible
Good spreadability Surgical and medical Lubricating
procedures
Greaseless (especially for Adherent to instrument
acne preparations) surfaces
Easily removed Maximal contact with
mucous membranes
Emollient Non-irritating
Demulcent (especially for Vaginal Acid stable
abraded tissue)
Non-staining Adherent
Compatible with a number Does not liquefy at body
of excipients temperature
Water soluble or miscible Greaseless and non-tacky
Nasal Adherent Lubricating
Odorless Slow dissolving
Non-irritating Non-irritating
Water soluble
Table 2: Favorable Properties of Pharmaceutical Gels [2].
Natural Polymers A Proteins

Gelatin
Collagen
B Polysaccharides:
Pectin
Gellum Gum
Alginic acid
Agar
Xanthin
Cassia tora
Tragacanth
Sodium or Potassium carrageenan
Guar Gum
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Semisynthetic polymers A Cellulose derivatives:

Methylcellulose
Hydroxyethyl cellulose
Hydroxypropyl cellulose
Carboxymethyl cellulose
Hydroxypropyl methyl cellulose
Synthetic Polymers A Carbomer:
Carbopol-934
Carbopol-940
Carbopol-941
B Polyacrylamide
C Poloxamer
D Polyvinyl alcohol
E Polyethylene and its co-polymers
Inorganic substances A Bentonite
B Aluminium hydroxide
Surfactants A Brij-96
B Cetostearyl alcohol
C Sodium lauryl sulphate
D Dodecyl pyridinium iodide
E Sorbitan mono-oleate
F Lecithin
Table 3: Gel Forming Substances [9,10].
Formulation Considerations for Pharmaceutical Gels [11]
The choice of vehicle/solvent

Normally purified water is used as a solvent. To enhance the solubility of the therapeutic agent in the dosage form and/or to improve
drug permeation across the skin, co-solvents may be used,
E.g., alcohol, glycerol, PG, PEG 400, etc.
Inclusion of buffers
Buffers may be involved in aqueous and hydroalcoholic-based gels to control the pH of the formulation. The solubility of buffer salts
is reduced in hydroalcoholic-based vehicles.
E.g., Phosphate, citrate, etc.
Preservatives
Certain preservatives cooperate with the hydrophilic polymers used to prepare gels, thereby reducing the concentration of free (anti-
microbially active) preservative in the preparation. Therefore, to compensate for this, the initial concentration of these preservatives
should be improved.
E.g., Parabens, phenolics, etc.
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Antioxidants
It may be involved in the formulation to improve the chemical stability of therapeutic agents that are prone to oxidative degradation. Its
choice is based on the nature of the vehicle used in the preparation of gel. Water-soluble antioxidants are generally used as the majority
of gels are aqueous-based.
E.g., Sodium metabisulphite, sodium formaldehyde sulfoxylate, etc.
Flavors/Sweetening agents
Flavors and sweetening agents are only incorporated in gels that are designed for administration into the oral cavity (E.g., for the treat-
ment of infection, inflammation, ulceration, etc.).
E.g.,
Sweeteners: Sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium, aspartame, etc.
Flavors: Butterscotch, apricot, peach, vanilla, wintergreen mint, cherry, mint, anise, citrus flavors, raspberry.
Manufacture of Gels [11]

Generally the water soluble excipients are firstly dissolved in vehicle, in a mixing vessel by using mechanical stirrer. To prevent
aggregation, add hydrophilic polymer to the stirred mixture slowly. Stirring is continued until the dissolution of the polymer has oc-
curred. The excessive stirring results in entrapment of air. The mixing rate must not be extreme or a mixing vessel may be used to which
a vacuum may be pulled, to prevent the entrapment of air.
Factors Affecting Topical Drug Delivery [12-15]

The success of topical drug delivery is dependent on the interplay among various factors:
a. Physiological factors
b. Physicochemical properties of the drug
c. Formulation components and their interactions
Physiological factors concern mainly the properties of the skin such as thickness, hydration level and hair follicle density. These
properties can demonstrate high individual variability depending on the age, gender, race, anatomical site, general health and environ-
ment condition such as temperature and humidity. In order to minimize the effects of such physiological variability, the rate-limiting
step for topical drug delivery should reside in the formulation instead of the biological barrier.
The drug physicochemical properties almost invariably influence its ease of diffusion through the topical vehicle as well as perme-
ation through the skin or mucosal surfaces. Properties of great significance include the molecular size as reflected by the molecular
weight, partition coefficient between the vehicle and skin, melting point, stability, and chemical functionality which influence ioniza-
tion potential, binding affinity and drug solubility in the vehicle.
The role of vehicle formulation is evident through its effect on the drug as well as the site of application. The effect on the drug
encompasses drug diffusion, thermodynamic activity, stability and degree of ionization of weakly acidic or basic drugs. The effect on
the site of application is associated with modification of barrier property via chemical changes imparted by simultaneous uptake of
formulation components and physical occlusion. These processes promote skin hydration or changes that increase drug penetration.
The formulation factor also has an impact on vehicle consistency and viscosity which in turn, determine the adhesion and retention
properties of the vehicle.
These properties were important to ensure vehicle retention in its site of application for effective drug delivery.
Topical vehicles can be broadly classified as liquids, semisolids and solids (Table 4). The semisolids are by far the most widely used
form of topical vehicles.
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System Monophase Diphase Multiphase

Liquid Non-polar solution Polar Emulsion (o/w, w/o) Emulsion (o/w/o, w/o/w)
solution Suspension Suspension
Semisolid Anhydrous ointment, nonpolar Emulsion (o/w, w/o) Emulsion (o/w, w/o)
ointment, polar ointment, Suspension with powder
Hydrogel, non-polar gel, polar gel
Solid Powder Transdermal patch Transdermal patch
Table 4: Classification of topical vehicles.
Evaluation Parameters of the Formulated Gels [9,16]
Measurement of pH
The pH was determined by using a digital pH meter. Dissolve 1g of gel in 100 ml of distilled water and stored for 2h. done the mea-
surement of pH in triplicate and calculate the average values.
Drug content
Mixed 1g of the gel with 100 ml of suitable solvent. Filter the stock solution. Then prepared the aliquots of different concentration
by suitable dilutions and measure the absorbance. Drug content was calculated by using the equation, which was got by linear regres-
sion analysis of calibration curve.
Viscosity study
It is carried out by using Brookfield viscometer. Rotated the gels at 0.3, 0.6 and 1.5 RPM. Note down the corresponding dial reading
at each speed. The viscosity was obtained by dial reading × factor given in the Brookfield viscometer catalogues.
Spreadability
It indicates the extent of the area to which gel readily spreads on application to the skin or affected part. The therapeutic potency
also depends upon spreading value. The time in sec taken by two slides to slip off from gel which is placed in between the slides under
the direction of certain load is expressed as spreadability. Lesser the time taken for the separation of two slides, better the spreadabil-
ity. The following formula is used to calculate the spreadability:
Spreadability (S) = M × L / T
Where,
M = weight tied to upper slide
L = length of glass slides
T = time taken to separate the slides
Extrudability study
The formulations are fill in the collapsible tubes, after it was set in the container. Extrudability is determine in terms of weight in
gm required to extrude a 0.5 cm ribbon of gel in 10 second.
Skin irritation study

For skin irritation study, Guinea pigs (400-500g; either sex) were used. The animals were maintained on the standard animal feed
and had free access to water. The animals were kept under standard conditions. Hair was shaved from the back. Five ml of each sample
was withdrawn periodically at 1,2,3,4,5,6,7 and 8h and each sample was replaced with an equal volume of fresh dissolution medium.
Then analyzed the samples for drug content by using phosphate buffer as guinea pigs and an area of 4 cm was marked blank on both
the sides, one side served as control while the other side was test. The gel was applied (500 mg/ guinea pig) twice a day for 7 days and
the site was observed for any sensitivity and the reaction if any. It was graded as:
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0 No reaction
1 Minor patchy erythema
2 Minor but confluent or modest but patchy erythema
3 Severe erythema with or without edema
In-vitro Diffusion studies

It can be carried out in a Franz diffusion cell, for studying the dissolution release of gels through a cellophane membrane. 0.5g of
gel sample was taken in cellophane membrane. Carried out the diffusion studies at 37 ± 1°C using 250 ml of phosphate buffer (pH 7.4)
as the dissolution medium.
In-vivo studies
Inhibition of carrageenan induced rat paw edema: 3 groups of 6 male Wistar albino rats were used.
Group Sample
1 Marketed sample (Reference)
2 For the test formulation
3 For control
Measure the volume of unilateral hind paw test animal. Before the carrageenan administration, rubbed 100 mg of preparation
carefully twice at 1 and 2h on each paw. Placed them in cages with copography meshes. Inject 0.1 ml of 1% w/v carrageenan subcuta-
neously into the paw. The volume of hind paw measured at hourly intermission for 5h. Use mercury plethysmometer for that. Calculate
the percentage of inhibition.
Stability
It was carried out by freeze-thaw cycling. Here, the product to a temperature of 4°C for 1 month, then at 25°C for 1 month and
then at 40°C for 1 month, syneresis was observed. Then the gel is exposed to ambient room temperature. Note the liquid exudate
separated.
Homogeneity
Set the gel in container and then it were tested for homogeneity by visual inspection. They were tested for their appearance and
presence of any aggregates.
Grittiness
The formulations were evaluated microscopically to check the presence of any visible particulate matter which was seen under
light microscope.
Sr. No. Patent No. Formulation

1 US 5939090 A Gel formulations for topical drug delivery
2 EP 1304992 B1 Topical gel delivery systems for treating skin disorders
3 US 5914334 A Stable gel formulation for topical treatment of skin conditions
4 EP 0183322 A2 Gel-form topical antibiotic compositions
5 WO 0187276 A1 Hydrogel composition for transdermal drug delivery
6 US 2014363498 A1 Hydrogel polymeric compositions and methods
7 US 8771734 B2 Sustained-release hydrogel preparation
8 US 2200709 A Organogel
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9 EP 2711001 A3 Organogel compositions and processes for producing

10 US 2327968 A Porous xerogel
11 US 8703284 B1 Aerogel/Xerogel composite material amalgamated with single-walled
carbon nanotubes for multipurpose usage
12 US 3033686 A Plastic gels of water and acyl lactylic acids and their salts
13 US RE35144 E Thixotropic adhesive gel
14 US 2487600 A Aqueous thixotropic gel composition
15 US 6117176 A Elastic-crystal gel
16 US 4643924 A Protective article comprising an elastic gel
17 US 6045814 A Cosmetic use of a rigid gel, and cosmetic or dermatological composi-
tions therefor
18 WO 2008014036 A1 Aqueous gel formulation and method for inducing topical anesthesia
19 US 20070031479 A1 Bioadhesive gel based on hydroxyethy cellulose
20 WO 2009042231 A2 Sol-gel phase-reversible hydrogel templates and uses thereof
Table 5: Patentable formulations [17-36].
S No. Active Ingredients Proprietary Gelling Agent Route & Use

1 Acetic acid Aci-jel Tragacanth, acacia Vaginal: restoration and
maintenance of acidity
2 Becaplermin Regranex Gel Na CMC Dermatologic
3 Benzoly peroxide Desquam-X Gel Carbomer 940 Acne vulgaris
4 Clobetasol Termovate Gel Carbomer 934 Antipruritic
5 Clindamycin Cleocin T Gel Carbomer Acne Vulgaris
6 Cyanocobalamin Nascobal Methyl Cellulose Nasal: Hematologic
7 Desoximetasone Topicort Gel Carbomer 940 Anti-inflammatory; antipruritic
8 Metronidazole Metro-Gel Carbomer Vaginal: Bacteria
9 Progesteron Suppliment Crinone-Gel Carbomer Progesteron
10 Tretinion Cellulose Retin-A Hydoxypropyl Cellulose Acne Vulgaris
Table 6: Examples of Gels.
Conclusion
Gels are getting more popular nowadays because they are more stable and also can provide controlled release than other semisolid
preparations like creams, ointments, pastes, etc. The gel formulation can provide better absorption characteristics and hence increase
the bioavailability of the drug. A thorough investigation into the stability characteristics of the gel formulation over an extended period
of time may provide scope for its therapeutic use for patients. Since the polymer is water soluble; consequently, it forms a water wash-
able gel and has wider prospects to be used as a topical drug delivery dosage form. The principal advantage of topical drug delivery lies
in targeting the drug action directly to the site of disorder by allowing accumulation of high local drug concentration within the tissue
and around its vicinity for enhanced drug action this is more effective when drugs with short biological half-life, narrow therapeutic
window are applied with topical route. The clinical evidence shows that topical gel is a safe and effective treatment choice for use in
the management of skin related diseases.
33-47.
46
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A Review on Pharmaceutical Gel

Article in International Journal of Pharmaceutical Sciences · October 2015

Hemendrasinh Rathod Dhruti Mehta

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A Review on Pharmaceutical Gel

Received: July 27, 2015; Published: September 30, 2015

Terminologies Related to Gels [1]

Structure of Gels [4]

Properties of Gels [1,2,4,6]

Characteristics of Gels [4,7]

Uses of Gels [7]

Classification of Gels [1,6,8]

Based on colloidal phases

Inorganic (Two phase system)

Organic (Single phase system)

Based on nature of solvent

Hydrogels (Water based)

Uses for hydrogels

1. Sustained-release drug delivery systems

Organogels (With a non-aqueous solvent)

Based on rheological properties

Based on physical nature

Preparation of Gels [8]

Substance Gel-forming Required additives

Table 1: Gelling Concentrations for Substances Used In Pharmaceutical Products [2].

Applications Favorable Applications Favorable properties

Table 2: Favorable Properties of Pharmaceutical Gels [2].

Natural Polymers A Proteins

Semisynthetic polymers A Cellulose derivatives:

Table 3: Gel Forming Substances [9,10].

Formulation Considerations for Pharmaceutical Gels [11]

The choice of vehicle/solvent

Manufacture of Gels [11]

Factors Affecting Topical Drug Delivery [12-15]

System Monophase Diphase Multiphase

Table 4: Classification of topical vehicles.

Evaluation Parameters of the Formulated Gels [9,16]

Skin irritation study

In-vitro Diffusion studies

Sr. No. Patent No. Formulation

9 EP 2711001 A3 Organogel compositions and processes for producing

Table 5: Patentable formulations [17-36].

S No. Active Ingredients Proprietary Gelling Agent Route & Use

Table 6: Examples of Gels.

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