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International Standard Serial Number (ISSN): 2319-8141
International Journal of Universal Pharmacy and Bio Sciences 2(5): September-October 2013
INTERNATIONAL JOURNAL OF UNIVERSAL
PHARMACY AND BIO SCIENCES
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REVIEW ARTICLE……!!!
Pharmaceutical Sciences
Received: 03-09-2013; Accepted: 21-09-2013
TOPICAL GEL CONTAINING ANTI FUNGAL AGENT
Phaldesai Saiesh *, A.R Shabaraya, Shripathy D, Leyana Soman.
Department of Pharmaceutics, Srinivas College of Pharmacy, Valachil, Mangalore, Karnataka.
KEYWORDS:
ABSTRACT
Topical infections, Topical
Over the past 30 years, greater attention has been focused on the
Gel, Polymers.
development of controlled and sustained drug delivery systems. The
For Correspondence:
Phaldesai Saiesh *
extensive research has been carried out in designing of polymeric drug
Address: Department of
Pharmaceutics, Srinivas
College of Pharmacy,
Valachil, Mangalore,
Karnataka.
Email:
delivery systems. The development of topical gel systems has received
considerable attention over the past few years. There is an increase in
the number of topical gel systems which have been investigated and
used on many patients for various biomedical applications. The topical
gel formulation offers an interesting alternative for achieving systemic
drug effects of parental routes, which can be inconvenient for oral route,
which can result in nausea, vomiting, and low bioavailability and passes
[email protected]
the hepatic first-pass metabolism. This novel drug delivery system
promotes the importantly ease and convenience of administration,
deliverance of accurate dose as well as to prolong residence time of
drug in contact with skin membrane. Smart polymeric system represents
promising means of delivering the drug. Various synthetic and natural
polymers are been used in the formulation of topical gels.
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International Standard Serial Number (ISSN): 2319-8141
INTRODUCTION:
The skin is one of the most extensive and readily accessible organs of the human body. The skin
of the average human being cover an area of about 2 square meter and weighs 4.5-5 kg, about 16
% of total body weight. It also receives 1/3rd of the total blood supply. The thickness of the
human skin ranges from 0.5 mm on the eyelids to 4 mm on the heels [2]. Superficial fungal
infections are among the most widespread diseases known to man. They target the parts of the
body as diverse in form and function as the skin, the nail, the buccal cavity, the eye and the
vagina. Fungistatic azole drugs, that is, imidazole and triazole-containing compounds, have been
the mainstay of antifungal therapy for many years. The imidazole derivative econazole nitrate is
effective in treating Candida albicans infections. Other new agents include the echinocandins (e.g.
caspofungin) that are primarily intended for systemic administration but which may have a role in
topical therapy [3]. Widely used topical formulations are ointments, creams, gels, lotions, pastes,
powders and plasters which offers several advantages such as good patient compliance, ease of
applying and removing, avoid inconvenience associated with intravenous therapy, eliminate the
problem of gastric irritation, termination of therapy is possible if toxicity is observed, they offer
alternative route in case of nausea and vomiting . Therefore it was found essential to find an
alternative, equally effective in topical drug delivery and economical in therapeutic work. The
aim of the research work is to formulate and evaluate gel containing Econazole Nitrate for topical
drug delivery to enhance the penetration efficacy of drug, reduction in drug toxicity, and
reduction in dosing frequency of the drug [5].
Advantages of the medicated soap strip: [6]
1. Avoids hepatic first-pass metabolism.
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2.
Maintains constant blood levels for longer period of time.
3.
Improves bioavailability.
4.
Decreases the dose to be administered.
5.
Decreases side or unwanted effects.
6.
Decreases gastrointestinal side effects.
7.
Easy to discontinue in case of toxic effects.
8.
Increased patient compliance.
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International Standard Serial Number (ISSN): 2319-8141
Classification: [7]: Gels are classified according to the following ways:
I.
According to source of gelling agent:
a. Natural gels
b. Synthetic gels
II. According to the liquid medium entrapped:
a.
Hydrogels
b. Organogels
III. According to their cross linkage:
a.
Chemical gels
b.
Physical gels
IV. According to the chemical nature of gelling agent:
a.
Organic gels
b.
Inorganic gel
Most natural gums such as acacia, carrageenan, and xanthan gum, are anionic polysaccharide that
yields natural gels. Number of cellulose derivatives have been synthesized and used as gallants
(e.g. sodium carboxymethylcellulose, hydroxyethylcellulose, Carbapol, hydroxyl propyl cellulose
etc.) that yield synthetic gels. The nature of the solvent also determines whether the gel is a
hydrogel (i.e. water based) or an organogel (i.e. with nonaqueous solvent).
Thus, bentonite magma and gelatin gel are hydrogels and dispersions of metallic stearates in oil
are examples of organogels. A hydrogel is a polymeric material that exhibits ability to swell in
water and absorb a significant fraction of water (2000 times the polymer weight) within its
structure without dissolving in water. A wide variety of natural materials of both plant and animal
origin, materials prepared by modifying naturally occurring structures, and synthetic polymeric
material are hydrogels.
Properties of Gels:
Gels should possess the following properties [8]:
1. Ideally, the gelling agent for pharmaceutical or cosmetic use should be inert, safe, and
should not react with other formulation components.
2. The gelling agent included in the preparation should produce a reasonable solid-like nature
during storage that can be easily broken when subjected to shear forces generated by
shaking the bottle, squeezing the tube, or during topical application.
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International Standard Serial Number (ISSN): 2319-8141
3. The gel should exhibit little viscosity change under the temperature variations of normal
use and storage.
4. It should possess suitable anti-microbial to prevent from microbial attack.
5. The topical gel should not be tacky.
6. The ophthalmic gel should be sterile.
7. It should be economical.
Structure of Gels [9]:
The rigidity of a gel arises from the presence of a network formed by the inter linking 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 gel. The individual particles
of hydrophilic colloid may consist of either spherical or anisometric aggregates of small
molecules, or single macro- molecules. 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. The cross-linking of macromolecules by
primary valency bonds provides a further mechanism for the formation of gel network. This
behaviour is exhibited by silicic acid gel, which consists of a three- dimensional network of Si-O
bonds. The force 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 liquefiction of gel6. Systems that exhibit this type of transition, such
as agar and gelatin gels, are termed thermal gels. In addition, the transition from gel state to a
colloidal dispersion may in some case be brought about by mechanical agitation. Systems, such as
bentonite and aluminum hydroxide gels, that exhibit this type of transition are termed thixotropic
gels.
Antifungal drugs: This medicated paper soap strip can be prepared by using following antifungal
drugs.
Antifungal drugs- classification:
1. Antibiotics
Polyenes : Amphotericin B, Nystatin, Hamycin.
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International Standard Serial Number (ISSN): 2319-8141
2. Antimetabolite : Flucytosine
3. Azoles:
a) Imidazoles : Clotrimazole, Econazole, Miconazole, Ketoconazole.
b) Triazoles : Fluconazole, Itraconazole.
4. Allylamine : Terbinafine
5. Other topical agents: Tolnaftate, Benzoic acid, Sodium thiosulfate.
Among these imidazoloes, triazoles, terbinafine and other topical agents can be used for
superficial fungal infections [10].
Preparation of topical gel containing Econazole nitrate [11]:
Gels were prepared by cold mechanical method
Step 1- Required quantity of polymer was weighed and it was sprinkled slowly on surface of
purified water for 2 hrs. After which it was continuously stirred by mechanical stirrer, till the
polymer soaked in the water.
Step 2- With continuous stirring, triethanolamine was added to neutralize the gel and it maintains
the pH of the gel. Now the appropriate quantity of DMSO (Dimethyl sulfoxide) was added to the
gel, which behaves as the penetration enhancer, followed by the required quantity of Econazole
Nitrate.
Step 3- Finally Methyl Paraben Was added was added to the gel with continuous stirring till drug
get dispersed in gel completely.
Evaluation of Formulated Gel
Gels were evaluated for their clarity, pH, viscosity, spreadability, skin irritation test, drug content,
in vitro diffusion studies and in vivo studies by using standard procedure. All studies were carried
out in triplicate and average values were reported.
1. Physical stability: [11]
Inspected visually for its colour, homogeneity, consistency, spread ability.
2. pH measurement: [12]
pH values of 1% aqueous solutions of the prepared gels were measured by a pH meter
3. Spreadability: [11]
For the determination of spreadability, excess of sample was applied in between two glass slides
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International Standard Serial Number (ISSN): 2319-8141
and was compressed to uniform thickness by placing 1kg weight for 5 min. weight (50 g) was
added to the pan. The time in which the upper glass slide moves over to the lower plate was taken
as measure of spread ability.
S = M.L / T
M- Weight tied to the upper slide
L - Length moved on the glass.
T - Time Taken
4. Homogeneity: [14]
All developed gels were tested for homogeneity by visual inspection after the gels have been set
in the container for their appearance and presence of any aggregate.
5. Extrudability study of the topical gel:
Measure the force required to extrude the material from tube. Extrudability was based upon the
quantity in percentage of gel and gel extruded from lacquered aluminium collapsible tube on
application of weight in grams required to extrude at least 0.5 cm ribbon of gel in 10 seconds.
6. In-vitro drug diffusion study of the prepared gel. [11]
The diffusion medium used was Phosphate buffer Ph 7.4, carried out using franz diffusion cell.
The diffusion cell was placed on the magnetic stirrer.; the outlet of the resorvior was maiuntained
at 37 c. The receptor compartment was filled with fluid (Phosphate buffer 7.4pH), Prehydrated
cellophane paper was used as the membrane. The speed of the stirrer was kept constant. With the
help of micropipette sample was taken for specified period of time.
7. Content uniformity:
Drug content of gel was determined by dissolving accurately weighed 1gm of gels in Methanol.
After suitable dilution absorbance was recorded by using UV- visible spectrophotometer (UV –
1700, Shimadzu, Japan) at 222 nm. Drug content was determined using slope of standard curve.
8. Viscosity measurement: [15]
The viscosity of the different gel formulations was determined at 25°C using a cone and plate
viscometer.
9. Determination of zone of inhibition: [16]
Antifungal and Antibacterial activity was checked by agar well diffusion method. In this method
a previously liquefied medium was inoculated with 0.2 ml of Fungal and Bacterial suspension
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International Standard Serial Number (ISSN): 2319-8141
having a uniform turbidity at temperature of 40 0C. 20 ml of culture medium was poured into the
sterile petri dish having a internal diameter of 8.5 cm. Care was taken for the uniform thickness
of the layer of medium in different plates. After complete solidification of liquefied inoculated
medium , the wells were made aseptically with cork borer having 6mm diameter. In each of these
plate extract and gel solution was placed carefully. Plates were kept for pre diffusion for 30 mins.
After it normalized to room temperature; the plates were incubated at 37ºc for 24 hrs in case of
bacteria and at 27ºc for 48 hrs in case of fungi. After incubation period was over, the zone of
inhibition was measured with help of Hi‐media.
10. Skin irritation study: [17]
In skin irritation study 10 rats of either sex weighing between (400‐500g) was used. Animals
were divided in to 2 groups of 5 animals each. Hairs were depleted from the back of rats with the
help of depilatories and area 4 cm2 was marked on both the sides. One side served as control
while the other as test and animals were used after 24 hrs. After hair depletion gel was applied
(500mg / rats) once a day for 7 days and site was covered with cotton bandage and observed for
any sensitivity and the reaction if any was graded as.
A ‐ No reaction, B ‐ Slight, patchy erythema, C ‐ Slight but confluent or moderate but patchy
erythema, D ‐ Moderate erythema, E ‐ Severe erythema with or without edema.
11. Stability Study [18]:
Short term accelerated stability study was carried out for the period of 45 days for the
formulations. The samples were stored at different storage conditions of room temperature,
elevated temperature such as 400C at 75% RH and refrigerator (2 to 80ºc). Samples was
withdrawn on weakly interval and analysed for visual appearance, clarity, pH and drug content.
CONCLUSION:
Topical infections are common and some of them are serious and even fatal. These infections
spreadable from person to person. There lies a need to control their growth using proper
antifungal medications. Various Dosage forms are available as strips, cream, soap, but these
medications have several disadvantages like economy, wastage, no accurate dosage, no proper
foam formation & contamination of soap. To prevent these side effects and problems, topical drug
delivery is one of the option as it is easy to carry, and any age group can accept it.
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