Experiment #

Object: Formulation development of Diclofenac potassium 1% emulgel

Requirements:
Measuring Cylinder, Mortar & Pestle, Magnetic stirrer, Spatula, Beaker,
Analytical balance, Glass rod
Theory:
Emulgels:
When gels and emulsions are used in a combined form the'dosage forms are
referred to as el. in emulgels. As the name suggests they are the combination of
emulsion/rnicroemulsion and g recent years, there has been great interest in the
use of novel polymers with complex functions as emulsifiers and thickeners
because the gelling capacity of these compounds allows the formulation of
stable emulsions by decreasing surface and interfacial tension and at the same
time increasing the viscosity of the aqueous phase.

Significance of Emulgels:

● The presence of a gelling agent in the water phase converts a classical

emulsion into an emulgel.
● Both oil-in-water and water-in-oil emulsions are used as vehicles to deliver
various drugs to the skin.

● Emulgels are able to deliver hydrophobic drugs to the systemic

circulation through the topical route.

● Emulgels for dermatological use have several favorable properties such

as being thixotropic, greaseless, easily spreadable, easily removable,
emollient, non-staining, water soluble, having longer shelf life, bio-
friendly, transparent, having and pleasing appearance.
 Advantages of Emulgel Disadvantages of Emulgel
1. Improved patient acceptability. ● Create problem in
absorption of
2. Offer targeted drug delivery. macromolecules.

3. Termination of the therapy at any time. ● Entrapment of air bubble during

formulation.
4. Enhance bioavailability as well as the
● Only hydrophobic drugs are
low doses can be effective in comparison with
the best choice for such delivery
other conventional semi solid preparation.
systems.
5. Became a stable formulation by
decreasing surface interfacial tension which
leads to increase the viscosity of aqueous
phase, more stable as compare to transdermal
preparations which are comparatively 1ess
stable.
6. Hydrophobic drug can be easily
incorporated in emulgel form by using
emulsion as the drug barrier which is finally
dispersed in to gel.

7. Provide the controlled effect of that helps

to prolong the effect of drug with short halflife.

8. Easy to formulate and cost effective

preparation.

9. Drug loading capacity is better than other

novel dosage forms like niosomes and
liposomes

10. Skin penetration is enhanced due to both

hydrophilic and hydrophobic nature

EMULSION: An emulsion may be defined aszphasic system consisting of two immiscible liquids.

one of

which (the dispersed phase) is finely and uniformly dispersed as globules throughout the
second phase (the continuous phase). Since emulsions are a thermodynamically unstable
system, a third agent, the emulsifier is added to stabilize the system. Emulsifier stabilizes the
system by forming a thin film around the ranges from 0.1 to globules of dispersed phase.
Pharmaceutical emulsions range from lotions (low viscosity) to (high viscosity). The particle
size of the dispersed phase commonly creams.
Types of Emulsions:
1. Oil in Water Emulsions/Aqueous Emulsions: If the oil droplets are dispersed throughout
the aqueous phase, the emulsion is termed oil-in-water (0/W). They are non-greasy and are
easily removable from the skin surface and they are used externally to provide cooling effect
and internally to also mask the bitter taste of oil. Water soluble drugs are more quickly
released from 0/W emulsion. 0/W emulsion give a positive conductivity test as water, the
external phase is a good conductor of electricity.
2. Water in Oil Emulsions/Greasy Emulsions: A system in which the water is
dispersed as globules in the oil continuous phase is termed water-in-oil emulsion (W/0). They
are greasy and not water washable and are used externally to prevent evaporation of the
moisture from the surface of skin e.g. cold cream. Oil soluble drugs are more quickly released
from W/O emulsion. They do not give positive conductive test as oils are not conductors.
3. Multi-Emulsions: They are complex systems in which 0/W emulsion
droplets
are dispersed in oily phase making 0/W/O Emulsion or vice versa making a W/0/W Emulsion.
Their pharmaceutical applications include taste masking, adjuvant vaccines, an immobilization
of enzymes and sorbent reservoir of overdose treatments, and sometimes for the
augmentation of external skin or dermal absorption. Multiple emulsions have been formulated
as cosmetics, such as skin moisturizer. Prolonged release can also be obtained by means of
multiple emulsions.
4. Micro-Emulsions: Micro-emulsions are systems consisting of water, oil and
surfactant, which constitute a single optically isotropic and thermodynamically stable liquid
solution.

METHODS OF PREPARING EMULSIONS:

● Phase Inversion method-

In this method, the aqueous phase is first added to the oil phase so as to form a W/0 emulsion.
At the inversion point, the addition of more water results in the inversion of emulsion which
gives rise to an 0/W emulsion.

● Continental or Dry Gum method-

Extemporaneously emulsions are usually made by continental or dry gum method. In this
method, the emulsion is prepared by mixing the emulsifying agent (usually acacia) with the oil
which is then mixed with the aqueous phase.

● Wet Gum method-

In this method, the proportion of the constituents is same as those used in the dry gum
method; the only difference is the method of preparation. Here, the mucilage of the
emulsifying agent (usually acacia) is formed. The oil is then added to the mucilage drop by
drop with continuous trituration.
EMULSIFYING AGENTS:

Emulsifying agent or surfactant may be defined as, "A compound that lowers the surface tension
and forms a film at the interface of two immiscible liquids making them miscible". The efficiency
of an emulsifying agent is related to its chemical structure, solubility, pH and physical properties.

TYPES OF EMULSIFIERS:

There are two types of emulsifying agents on the basis of their effect;
1. Primary agents (true emulsifying agents) can form and stabilize emulsions by themselves
e.g. Sodium Lauryl Sulfate, Tweens, Esters of Stearic Acid, etc.

2. Auxiliary agents (stabilizers) alone do not form fine emulsions but assist the primary
emulsifying agents e.g. Tragacanth, Pectin, Acacia, Starch, Gelatin, etc. They are usually used as
viscosity modifiers.

MECHANISM OF EMULSIFYING AGENTS:

1. Monomolecular Films-

Emulsifiers make an interfacial film at the oil-water interface to prevent coalescence.

2. Multi-molecular Films-
In greater concentrations, hydrophilic colloids make a film around the dispersed globule to
prevent coalescence and enhance miscibility.

3. Solid Particle Films-

Inorganic molecules like Bentonite, Aluminum Hydroxide, Magnesium Trisilicate etc. can also
form solid particulate films at the interface of the dispersed system in the medium preventing
the interaction of the globules from one another and enhancing dispersion in the system.
 PROBLEMS IN EMULSION SYSTEMS:

- It is a function of chemical
- Water droplets falling from an structure and surfactant
Sedimentatio adsorption.
emulsion,
n - Due to the difference in oil and
which normally occurs due to the
difference in water density.
water and oil density.
- It is a function of chemical
- Not an actual breaking, but the structure and surfactant
CrHieaming adsorption.
separation of
emulsion into the denser part (cream) - Due to the difference in oil and
and the water density.
other parts.
- It depends on the surfactant
structure.
- It exhibits grouping of individual - It is the first step towards
Flocculation further emulsion ageing and
suspended
droplets together while each droplet coalescence.
keeps its - More frequent mechanisms in
identity. oil/water emulsions.

- It represents the mechanism by which - It is affected by the interfacial

Coalescence two or film viscosity, surfactant film
more separate groups of miscible elasticity, and the dynamics of
particles are thin liquid film drainage.
active as they pull each other to reach
the
slightest contact.
- It corresponds to formation of - It is the most common process,
Aggregation accumulated resulting in the destabilization of
droplets in a suspension. colloidal systems.
- It represents the diffusion of droplets - Generally experienced in
Ostwald into the water/oil emulsions.
ripening continuous phase to describe the - It is observed in liquid droplets
inhomogeneous structure modification or solid solutions.
such as
the re-deposition of surfactant particles
into
 larger particles over time.

Phase - It is defined as a complete separation - It is a function of time and

separation of oil and emulsifier type.
water into two distinct phases.

Gels:-
There are different semisolid dosage forms that are used for topical applications
among which gels formulations are becoming pre-eminent. Gels are semisolid
preparations intended for application on the skin or the accessible mucous
membranes like oral cavity. Gels are composed of two interpenetrating systems
where the colloidal particles, also known as the gelator or gallant, are uniformly
distributed throughout a dispersion medium or solvent forming a three
dimensional matrix known as the gel.

The basic network of gel is a combination of a gelling agent and a solvent in which
the drug molecules are embedded or entwined evenly."

Advantages of Gels :

Gels are easy to formulate as compared to other semisolid dosage forms.

A gel is an elegant non-greasy formulation.

iii) it can be used as controlled release formulation by entwining the polymer more
than once

iv) Gels have good adherence property to the site of application.

v) They are biodegradable and biocompatible.

vi) The retention time of gels is higher than other topical dosage forms.

vii) They have excellent tolerability to certain stress conditions.

viii) They form a protective layer on the application site.

ix) They are washable and nontoxic in nature.

x) They provide excellent spreadibility and cooling effect because of solvent

evaporation.

xi) They have comparatively less long term stability issues.

x) They can be used to administer both polar and non-polar drugs.

Disadvantages of Gels :-

(i) The effect of gels is comparatively slower and sustained.

ii) The additives or the gelators may induce irritation.

The water content may increase the chances of microbial or fungal attack in gels.

iv) Syneresis (expulsion of solvent from the gel matrix) may occur in gels during
storage.

v) Solvent evaporation from the formulation may result in drying of the gel.

vi) Covalent bonds present in some gels may render them unbreakable thus
sealing the medicament inside the gel matrix.

vii) Flocculation in some gels may produce an unstable gel.

vili) Rheology of some gels may alter due to the effect of temperature, humidity
and other environmental factors.

ix) The gelling agents may precipitate and result in salting out.

Some drugs may degrade in gel formulation due to the presence of polymers.

Types of Gels :

They are classified into different categories on the basis of the following criteria;
1. Nature of colloid phase

a. Inorganic gels (Two phase system)

b. Organic gels (single phase system)

2. Based on nature of solvent

a. Hydrogel (Aqueous gels)- Gels that consist of an aqueous dispersion medium

that is gelled with a suitable hydrophilic gelling agent are known as hydrogels. By
definition, hydrogels are polymeric networks with three-dimensional configuration
capable of imbibing high amounts of water or biological fluids. Their affinity to
absorb water is attributed to the presence of hydrophilic groups such as OH,
CONH-, -CONH2-, and-SO3H in polymers forming hydrogel structures.

b. Xerogel-It is a solid formed from a gel by drying with unhindered shrinkage.

Xerogels usually retain high porosity (15-50%) and enormous surface area (150-
900 m²/g), along with very small pore size (1-10 nm).

c. Organic gel (Non aqueous gels)- Organogels may also be referred as oleaginous
gels. They are composed of both polar and nonpolar groups but the ratio of the
non-polar part is very high. They may contain 35% water as the gels tend to swell in
water. Organogelators are usually low molecular weight small molecules that have
the ability to thicken in organic solvents.

3. 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

4. Based on physical nature

a. Elastic gel

b. Rigid gel

Classes of Gelling Agents

1. Natural Polymers:

a. Proteins-Collagen,
Gelatin

b. Polysaccharides -
Agar, Alginate acid, Sodium or Potassium carageenan, Tragacanth, Pectin, Guar
Gum, Cassia tora, Xanthan, Gellum Gum

2. Semisynthetic polymers cellulose derivatives:

Carboxymethyl cellulose, Methylcellulose, Hydroxyethyl cellulose Hydroxypropyl
cellulose, Hydroxy propyl (methyl cellulose),

3. Synthetic polymers:

a. Carbomer-Carbopol 940,

b. Carbopol 934

c. Polyacrylamide

d. Poloxamer

e. Polyvinyl alcohol

f. Polyethylene and its copolymers

4. Inorganic substances:

a. Bentonite

b. Aluminium hydroxide

5. Surfactants:

a. Cebrostearyl alcohol

b. Brij-96

Properties and characteristics of Gel:

 Swelling:
When a gelling agent is left in contact with a liquid that solvates it then a
considerable amount of liquid is absorbed by the agent and the volume increases.
This process is called swelling.
Syneresis: many gels often contact spontaneously on standing and exude some
fluid medium. This effect is known as syneresis.The degree to which syneresis
occurs increases as the concentration of gelling agent decreases.
Ageing: colloidal systems usually slow show aggregation naturally.This process is
known as ageing.In gels, ageing causes gradual formation of a denser network of
the gelling agent.
Structure: The rigidity in a gel results due to the presence of a network formed by
the interlinking of particles of the gelling agents. The nature of the particle and the
stress, straighten them out and decrease the resistance to flow.
Rheology: Solution of the gelling agents and dispersion of flocculanted solid are
pseudo plastic in nature follow Non-Newtonian flow behavior, characterized by a
reduction in viscosity with increase in shear rate.

Mechanism of gelling agent :

1) Chemical cross linking: These polymer are usually in solvent but certain
solvent when incorporated results results in swelling and forming a gel. For
example polyacrylamide gels. These gels are covalently bonded and
Irreversible in nature .chemical cross linking can be obtained with polymers
having un bonded groups in their structures.
2) Physical cross linking: In some cases solutions to gel transition can rake
place by hydrogen bonded formation, crystalline components solubilization,
concentration variation, temperature variation transition or hydrophobic
interaction. For example dextram gels , poky ( N isopropyl lacrylamide ) gels
,cellulose gels .
3) Ionic cross linking : Cross linking can also be achieved by forming charges
on polymer or other molecule that may attract each other to form a gel.
Ionic bonds are formed as a result of the charges on such molecule. For
example polysaccharide alginate in presence of calcium ions produces a
gel matrix which can encapsulate certain components.
Diclofenac potassium is a nonsteroidal anti-inflammatory drug
(NSAID) with various uses:

*Therapeutic Uses:*
1. Pain relief: mild to moderate pain, inflammation, and fever.
2.Osteoarthritis: relieves pain, inflammation, and stiffness.
3. Rheumatoid arthritis: reduces joint pain, swelling, and morning stiffness.
4. Ankylosing spondylitis: manages spinal pain and inflammation.
5. Menstrual cramps (dysmenorrhea): alleviates pain and inflammation.
6. Migraines: treats acute migraine attacks.
7. Post-operative pain: manages pain after surgery.
Marketed products:

1) Voltral emulgel ( Novartis)

2) Index gel ( GSK)
 3) Froben gel ( Abbott)
4) Dicloran gel ( sami)
5) Clinagel (stiefel)

FORMULATION

Emulgel

Ingredients Quantity Role of ingredients

Aquabase cream 80g Emulsifier
1% CMC gel 20g Gel base
Diclofenac 0.5g Antiinflammatory/
potassium Analgesic

Aquabase cream

Ingredients Quantity Role of ingredients

Cebrostearyl alcohol 13% Emulsifier
White soft paraffin 5% Base

Butylated Hydroxy 10% Antioxidant

toulene
Meyhyl parabin 0.25% Preservative
Propyl parabin 0.15% Preservative
EDTA 0.1% Preservative
Water q.s 100g Vehicle

CMC gel

Ingredients Quantity Role of ingredients

CMC 1g Thickner/ gelling
agent
Sodiumbenzoate 0.1% Preservative
Water q.s 100g Vehicle
Procedure
Preparation of CMC gel
In 100ml of Beaker add 0.1g of sodium benzoate and add 60ml water
Keep this Beaker on magnetic stirrer until all the mixture is dissolved
Add 1g of CMC and mix well with rapid and through mixing with the
help of glass rod
Leave the gel on bench for 2 hours . It will help to dissolve any
remaining lumps
Check the consistency of gel and make up the volume with 100ml
water

Preparation of aquabase cream

In a beaker dissolve methyl parabin,propyl parabin and EDTA with
water
In another Beaker dissolve cebrostearyl alcohol, White soft paraffin
and Butylated Hydroxy toulene
Keep this Beaker on magnetic stirrer at 80c until it melt
Now stop heating and mix both the mixture at 60c rapidly with the
help of glass rod

Preparation of diclofenac potassium emulgel

For 50g of emulgel mix 40g of aqua base cream and 10g of CMC gel
and mix thoroughly
Incorporate 0.5g of diclofenac potassium in the emulgel and mix well

Result

Discussion