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Many advantages of gels a major limitation is in the delivery of hydrophobic drugs. So to overcome this
limitation an emulsion based approach is being used so that even a hydrophobic therapeutic moiety can enjoy
the unique properties of gels. When gels and emulsions are used in combined form the dosage form are referred
as emulgel. In recent years, there has been great interest in the use of novel polymers. A unique aspect of
dermatological pharmacology is the direct accessibility of the skin as a target organ for diagnosis and
treatment. The combination of hydrophilic cornified cells in hydrophobic intercellular material provides a
barrier to both hydrophilic and hydrophobic substances. Within the major group of semisolid preparations, the
use of transparent gels has expanded both in cosmetics and in pharmaceutical preparations. Polymer can
function as emulsifiers and thickeners because the gelling capacity of these compounds allows the formulation
of stable emulsions and creams by decreasing surface and interfacial tension and at the same time increasing the
viscosity of the aqueous phase. In fact, the presence of a gelling agent in the water phase converts a classical
emulsion into an emulgel. These emulgel are having major advantages on novel vesicular systems as well as on
conventional systems in various aspects. Various permeation enhancers can potentiate the effect, So emulgels
can be used as better topical drug delivery systems over present systems. The use of emulgels can be extended in
analgesics and antifungal drugs.
INTRODUCTION
Topical drug administration is a localized drug
delivery system anywhere in the body through
ophthalmic, rectal, vaginal and skin as topical ro
utes. These are apply a wide spectrum
of preparations for both cosmetic and
dermatological, to their healthy or diseased skin.1
These formulations range in physicochemical
nature from solid through semisolid to liquid.
Drug substances are seldom administered alone,
but rather as part of a formulation, in combination
with one or more non medicated
agents that serve varied and specialized pharmac
eutical function. Drugs are administered topically
for their action at the site of application or for
systemic effects.2 Drug absorption through the skin
is enhanced if the drug substance is in solution, if it
has a favourable lipid/water partition coefficient and
if it is a nonelectrolyte. For the most part,
pharmaceutical preparations applied to the skin are
intended to serve some local action and as such are
formulated to provide prolonged local contact with
minimal systemic drug absorption. Drug applied to
the skin for their local action include antiseptics,
antifungal agent, skin emollients and protectant. The
main advantages of topical delivery system is to
bypass first pass metabolism. Avoidance of the risks
Asian Journal of Pharmacy and Life Science ISSN 2231 – 4423
Vol. 1 (3), July-Sept, 2011
334 | P a g e Available online on www.ajpls.com Review Article
334
and inconveniences of intravenous therapy and of
the varied conditions of absorption like pH changes,
presence of enzymes, gastric emptying time are
other advantages of topical preparations.3-4 The
topical drug delivery system is generally used
where the others system of drug administration f
ails or it is mainly used in fungal infection. Hu
man skin is a uniquely engineered organ that perm
its terrestrial life by regulating heat and water
loss from the body whilst preventing the ingress
of noxious chemicals or microorganisms. It is al
so the largest organ of the human body, providi
ng around 10% of the body mass of an average
person, and it covers an average area of 1.7 m2.
Whilist such a large and easily accessible organ
apparently offers ideal and multiple sites to adm
inister therapeutic agents for both local and syst
emic actions, human skin is a highly efficient
self‐repairing barrier designed to keep the inside
s in and the outside out.5 Gels are a relatively newer
class of dosage form created by entrapment of large
amounts of aqueous or hydroalcoholic liquid in a
network of colloidal solid particles, which may
consist of inorganic substances, such as aluminum
salts or organic polymers of natural or synthetic
origin.6 They have a higher aqueous component that
permits greater dissolution of drugs, and also permit
easy migration of the drug through a vehicle that is
essentially a liquid, compared with the ointment or
cream base.7 These are superior in terms of use and
patient acceptability. In spite of many advantages of
gels a major limitation is in the delivery of
hydrophobic drugs. So to overcome this limitation,
emulgels are prepared and used so that even a
hydrophobic therapeutic moiety can enjoy the
unique properties of gels.
In fact, the presence of a gelling agent in the water
phase converts a classical emulsion into an
emulgel.12 Both oil-inwater and water-in-oil
emulsions are used as vehicles to deliver various
drugs to the skin. Emulgels for dermatological use
have several favorable properties such as being
thixotropic, greaseless, easily spreadable, easily
removable, emollient, nonstaining, long shelf life,
bio-friendly, transparent & pleasing appearance.1
Use of topical agents requires an appreciation of the
factors that influence percutaneous absorption.14
Molecules can penetrate the skin by three routes:
through intact stratum corneum, through sweat
ducts, or through sebaceous follicle. The surface of
the stratum corneum presents more than 99% of the
total skin surface available for percutaneous drug
absorption.15
Passage through this outer most layer is the ratelimiting
step for percutaneous absorption. The
major steps involved in percutaneous absorption
include the establishment of a concentration
gradient, which provides the driving force for drug
movement across the skin, release of drug from the
vehicle (partition coefficient), and drug diffusion
across the layers of the skin (diffusion coefficient).
Preferable characteristics of topical drugs include
low molecular mass (600 Da), adequate solubility
in oil and water, and a high partition coefficient.
Except for very small particles, water soluble ions
and polar molecules do not penetrate intact stratum
corneum. Topical formulation can be used to
manipulate the barrier function of the skin, for
example, topical antibiotics and antibacterials help a
damaged barrier toward off infection, sun
screening agents and the horny layer protect the
viable tissues from Ultraviolet radiation and
emollient preparations restore pliability to a
desiccated horny layer.16
During development of semi-solid preparations for
cutaneous application whose formulation contains
an antimicrobial preservative, the need for and the
efficacy of the chosen preservative shall be
demonstrated to the satisfaction of the competent
authority. A suitable test method together with
Asian Journal of Pharmacy and Life Science ISSN 2231 – 4423
Vol. 1 (3), July-Sept, 2011
335 | P a g e Available online on www.ajpls.com Review Article
335
criteria for judging the preservative properties of the
formulation are provided in efficacy of antimicrobial
preservation. Sterile semi-solid preparations for
cutaneous application are prepared using materials
and methods designed to ensure sterility and to
avoid the introduction of contaminants and the
growth of microorganisms.17
The efficacy of an antimicrobial preservative may be
enhanced or diminished by the active constituent of
the preparation or by the formulation in which it is
incorporated or by the container and closure used.
Preparation for topical use should have
mircobiologial quality and it is checked with test for
sterility. Total viable aerobic count should not be
more than 102 micro-organisms (aerobic bacteria
plus fungi) per gram. It should not have more than
101 enterobacteria, certain other gram-negative
bacteria per gram and completely devoid of
Pseudomonas aeruginosa and Staphylococcus
aureus.18-19
This project is to reveal the material and method
used does’nt imparts any microbial contamination
and the methyl paraben 0.2% used is sufficient to
maintain its sterility. (micro biology)
RATIONALE
Many widely used topical agents like ointment,
cream, lotion have many disadvantages. They have
very sticky causing uneasiness to the patient when
applied. Moreover they also have lesser spreading
coefficient and need to apply with rubbing . And
they exhibit the problem of stability also. Due to all
these factors within the major group of semisolid
preparations, the use of transparent gels has
expanded both in cosmetics and in pharmaceutical
preparations.
A gel is colloid that is typically 99% wt liquid,
which is immobilized by surface tension between it
and a macromolecular network of fibers built from
a small amount of a gelating substance present. In
spite of many advantages of gels a major limitation
is in the delivery of hydrophobic drugs. So to
overcome this limitation an emulsion based
approach is being used so that even a hydrophobic
therapeutic moiety can be successfully incorporated
and delivered through gels.20
Important Constituents of Emulgel Preparation
1. Aqueous Material:
This forms the aqueous phase of the emulsion.
Commonly used agents are water, alcohols.28
2. Oils:
These agents form the oily phase if the emulsion.
For externally applied emulsions, mineral oils, either
alone or combined with soft or hard paraffins, are
widely used both as the vehicle for the drug and for
their occlusive and sensory characteristics. Widely
used oils in oral preparations are nonbiodegradable
mineral and castor oils that provide a local laxative
effect, and fish liver oils or various fixed oils of
vegetable origin (e.g., arachis, cottonseed, and
maize oils) as nutritional supplements.29-30
3. Emulsifiers:
Emulsifying agents are used both to promote
emulsification at the time of manufacture and to
control stability during a shelf life that can vary
from days for extemporaneously prepared emulsions
to months or years for commercial preparations.eg
Polyethylene glycol 4031 stearate, Sorbitan monooleate
32 (Span 80), Polyoxyethylene sorbitan
monooleate (Tween 80)33, Stearic acid34, Sodium
stearate.35
4. Gelling Agent:
These are the agents used to increase the consistency
of any dosage form can also be used as thickening
agent.36-37
5. Permeation Enhancers:
These are agents that partition into and interact with
skin constituents to induce a temporary and
reversible increase in skin permeability.38
EMULGEL PREPARATION
Emulgel was prepared by the method reported by
Mohammad et al (2004) with minor modification.
The Gel in formulations were prepared by
dispersing Carbopol 934 in purified water with
constant stirring at a moderate speed and Carbopol
940 in purified water with constant stirring at a
moderate speed then the pH are adjusted to 6 to 6.5
using Tri ethanol amine (TEA).
The oil phase of the emulsion were prepared by
dissolving Span 20 in light liquid paraffin while the
aqueous phase was prepared by dissolving Tween
20 in purified water. Methyl and Propyl paraben
was dissolved in propylene glycol whereas drug
was dissolved in ethanol and both solutions was
Asian Journal of Pharmacy and Life Science ISSN 2231 – 4423
Vol. 1 (3), July-Sept, 2011
338 | P a g e Available online on www.ajpls.com Review Article
338
mixed with the aqueous phase. Both the oily and
aqueous phases were separately heated to 70° to
80°C; then the oily phase were added to the aqueous
phase with continuous stirring until cooled to room
temperature. And add Glutaraldehyde in during of
mixing of gel and emulsion in ratio 1:1 to obtain the
emulgel.39
CHARACTERIZATION OF GELLIFIED
EMULSION
Physical appearance: The prepared Emulsion
formulations were inspected visually
for their color, homogeneity, consistency and pH.
The pH values of 1% aqueous solutions of the
prepared Gellified Emulsion were measured by a pH
meter (Digital pH meter DPH 115 pm).40
Spreadability: Spreadability is determined by
apparatus suggested by Mutimer et al (1956) which
is suitably modified in the laboratory and used for
the study. It consists of a wooden block, which is
provided by a pulley at one end. By this method,
spreadability is measured on the basis of ‘Slip’ and
‘Drag’ characteristics of emulgels. A ground glass
slide is fixed on this block. An excess of emulgel
(about 2 gm) under study is placed on this ground
slide. The emulgel is then sandwiched between this
slide and another glass slide having the dimension of
fixed ground slide and provided with the hook. A 1
Kg weight is placed on the top of the two slides for
5 minutes to expel air and to provide a uniform film
of the emulgel between the slides. Excess of the
emulgel is scrapped off from the edges. The top
plate is then subjected to pull of 80 gms. With the
help of string attached to the hook and the time (in
seconds) required by the top slide to cover a distance
of 7.5 cm be noted. A shorter interval indicate better
spreadability. Spreadability was calculated by using
the formula,
S= M.L/T
Where, S = spreadability,
M = Weight tied to upper slide,
L = Length of glass slides
T = Time taken to separate the slides
completely from each other.
Extrudability study:
It is a usual empirical test to measure the force
required to extrude the material from tube. The
method applied for determination of applied shear in
the region of the rheogram corresponding to a shear
rate exceeding the yield value and exhibiting
consequent plug flow. In the present study, the
method adopted for evaluating emulgel formulation
for extrudability is based upon the quantity in
percentage of emulgel and emulgel extruded from
lacquered aluminum collapsible tube on application
of weight in grams required to extrude at least 0.5
cm ribbon of emulgel in 10 seconds. More quantity
extruded better is extrudability. The measurement of
extrudability of each formulation is in triplicate and
the average values are presented. The extrudability
is than calculated by using the following formula:
Extrudability = Applied weight to extrude emulgel
from tube (in gm) / Area (in cm2)
Globule size and its distribution in emulgel:
Globule size and distribution was determined by
Malvern zetasizer. A 1.0 gm sample was dissolved
in purified water and agitated to get homogeneous
dispersion. Sample was injected to photocell of
zetasizer. Mean globule diameter and distribution
was obtained.43
Asian Journal of Pharmacy and Life Science ISSN 2231 – 4423
Vol. 1 (3), July-Sept, 2011
339 | P a g e Available online on www.ajpls.com Review Article
339
Rheological Study:
The viscosity of the different emulgel formulations
is determined at 25°C using a cone and plate
viscometer with spindle 52 (Brookfield Engineering
Laboratories,) and connected to a thermostatically
controlled circulating water bath.
Swelling Index:
To determine the swelling index of prepared topical
emulgel, 1 gm of gel is taken on porous aluminum
foil and then placed separately in a 50 ml beaker
containing 10 ml 0.1 N NaOH. Then samples were
removed from beakers at different time intervals
and put it on dry place for some time after it
reweighed. Swelling index is calculated as follows:
Swelling Index (SW) % = [(Wt – Wo) / Wo] × 100.
Where, (SW) % = Equilibrium percent swelling,
Wo = Original weight of emulgel at zero time
after time t, Wt = Weight of swollen emulgel
Ex–vivo Bioadhesive strength measurement of
topical emulgel:
(MICE SHAVEN SKIN): The modified method is
used for the measurement of bioadhesive strength.
The fresh skin is cut into pieces and washed with 0.1
N NaOH. Two pieces of skin were tied to the two
glass slide separately from that one glass slide is
fixed on the wooden piece and other piece is tied
with the balance on right hand side. The right and
left pans were balanced by adding extra weight on
the left-hand pan. 1 gm of topical emulgel is placed
between these two slides containing hairless skin
pieces, and extra weight from the left pan is
removed to sandwich the two pieces of skin and
some pressure is applied to remove the presence of
air. The balance is kept in this position for 5
minutes. Weight is added slowly at 200 mg/ min to
the left-hand pan until the patch detached from the
skin surface. The weight (gram force) required to
detach the emulgel from the skin surface gave the
measure of bioadhesive strength. The bioadhesive
strength is calculated by using following:
Bioadhesive Strength = Weight required (in gms) /
Area (cm2)
Figure :1Setup for bioadhesive test
Drug Content Determination:
Drug concentration in Gellified Emulsion was
measured by spectrophotometer. Drug content in
Gellified Emulsion was measured by dissolving
known quantity of Gellified Emulsion in solvent
(methanol) by Sonication. Absorbance was
measured after suitable dilution in UV/VIS spectrop
hotometer (UV‐1700 CE, Shimadzu Corporation, Ja
pan).46
In Vitro Release Study:
Franz diffusion cell (with effective diffusion area
3.14 cm2 and 15.5 ml cell volume) was used
for the drug release studies. Gellified Emulsion
(200 mg) was applied onto the surface of egg
membrane evenly. The egg membrane was clam
ped between the donor and the receptor chamber
of diffusion cell. The receptor chamber was fill
ed with freshly prepared PBS (pH 5.5) solution
to solubilize the drug. The receptor chamber wa
s stirred by magnetic stirrer. The samples (1.0 ml
aliquots) were collected at suitable time interval. Sa
mples were analyzed for drug content byUV visible
Asian Journal of Pharmacy and Life Science ISSN 2231 – 4423
Vol. 1 (3), July-Sept, 2011
340 | P a g e Available online on www.ajpls.com Review Article
340
spectrophotometer
after appropriate dilutions. Cumulative corrections
were made to obtain the total amount of drug rel
ease at each time interval .The cumulative amou
nt of drug released across the egg membrane was d
etermined as a function of time.47
Microbiological assay:
Ditch plate technique was used. It is a techniqu
e used for evaluation of bacteriostatic or
fungistatic activity of a compound. It is mainly
applied for semisolid formulations. Previously pr
epared Sabouraud’s agar dried plates were used.
Three grams of the Gellified Emulsion are placed
in a ditch cut in the plate. Freshly prepared culture
loops are streaked across the agar at a right ang
le from the ditch to the edge of the plate. After
incubation for 18 to 24 hours at 25°C, the fung
al growth was observed and the percentage inhi
bition was measured as follows.
% inhibition = L2 / L1 × 100
Where L1 = total length of the streaked culture
, and
L2 =length of inhibition.
Skin irritation test:
A 0.5 gm sample of the test article was then appl
ied to each site (two sites per rabbit) by
introduction under a double gauze layer to an area
of skin approximately 1” x 1” (2.54 x 2.54 cm2
). The Gellified Emulsion are applied on the skin of
rabbit. Animals were returned to their cages. Afte
r a 24 hour exposure, the Gellified Emulsion ar
e removed. The test sites were wiped with tap
water to remove any remaining test article residue.
Accelerated stability studies of Gellified
Emulsion:
Stability studies were performed according to ICH
guidelines. The formulations were stored in hot air o
ven at 37 ± 2°, 45 ± 2° and 60 ± 2° for a period
of 3 months. The samples were analyzed for
drug content every two weeks by UV‐Visible spectr
ophotometer. Stability study was carried out by mea
suring the
change in pH of gel at regular interval of time.48
CONCLUSION
In the coming years, topical drug delivery will be
used extensively to impart better patient
compliance. Since emulgel possesses an edge in
terms of spreadibilty, adhesion, viscosity and
extrusion, they will become a popular drug delivery
system. Moreover, they will become a solution for
loading hydrophobic drugs in an water soluble gel
bases.