Topical Gel : A Review
Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system.
The skin of an average adult body covers a surface area approximately 2m2 and receives about one third of the blood circulating through the body. An average human skin surface is known to contain, on the average 40-70 hair follicles and 200-300 sweat ducts on every square centimeter of the skin. Although skin has been divided histologically into the stratum corneum, the living epidermis and the dermis, collectively it can be considered a laminate of barrier, permeation of this laminate can occur by diffusion via:
Transcellular penetration (across the cells)
Intracellular penetration (between the cells)
Transappendageal penetration (via hair follicles, sweat and sebum glands).
A myriad of medicated product are applied to the skin or readily accessible mucous membrane that in some way either augment or restore a fundamental function of a skin or pharmacologically modulate an action in the underlined tissues. Such products are referred as topical or dermatological product.
Rational Approach To Topical Formulations
Topical formulation can be used to:
Manipulate the barrier function of the skin, for example, topical antibiotics and antibacterials help a damaged barrier to ward off infection, sun screening agents and the horny layer protect the viable tissues from U.V. radiation and emollient preparations restore pliability to a desiccated horny layer. Direct drugs to the viable skin tissues without using oral, systematic or other routes of therapy. For example, anaesthetic, anti-inflammatory, antipruritic and antihistaminics drugs are to be delivered to viable epidermis and dermis.For skin appendage treatment, for example, antiperspirants, exfolients and depilatories are to be delivered to the skin appendages.Deliver drugs for systematic treatment, for example, transdermal therapeutic systems provide systemic therapy for motion sickness, angina and hypertension.
Classification Of Medicated Application For The Skin
Topical powders (dusting powders)
Transdermal drug delivery systems
Tapes and Gauzes
Out of above, gels are becoming more popular due to ease of application and better percutaneous absorption.
The term “Gel” was introduced in the late 1800 to name some semisolid material according to pharmacological, rather then molecular criteria.
The U.S.P. defines gels as a semisolid system consisting of dispersion made up of either small inorganic particle or large organic molecule enclosing and interpenetrated by liquid. The inorganic particles form a three-dimensional “house of cards” structure. Gels consist of two-phase system in which inorganic particles are not dissolved but merely dispersed throughout the continuous phase and large organic particles are dissolved in the continuous phase, randomly coiled in the flexible chains.
Gels are classified mainly by two methods based on:
a) Nature of colloid phase
i) Inorganic gels
ii) Organic gels
b) Based on nature of solvent
i) Aqueous gels
ii) Non aqueous gels
Gel forming substances
Polymers are used to give the structural network, which is essential for the preparation of gels. Gel forming polymers are classified as follows:
1. Natural polymer
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, Hydroxypropyl cellulose, Hydroxy propyl (methyl cellulose), Hydroxyethyl cellulose.
3. Synthetic polymers
A) Carbomer: Carbopol 940, Carbopol 934
D) Polyvinyl alcohol
E) Polyethylene and its co-polymers
4. Inorganic substances
A) Aluminium hydroxide
A) Cebrotearyl alcohol
B) Brij – 96
The topical administration of drug in order to achieve optimal cutaneous and percutaneous drug delivery has recently gain an importance because of various advantages:
They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH
and enzymatic activity and drug interaction with food and drinks.
They can substitute for oral administration of medication when that route is unsuitable.
To avoid the first pass effect, that is, the initial pass of drug substance through the
systemic and portal circulation following gastrointestinal absorption, possibly avoiding
the deactivation by digestive and liver enzyme.
They are non-invasive and have patient compliance.
They are less greasy and can be easily removed from the skin.
Reduction of doses as compare to oral dosage forms.
Localized effect with minimum side effects.
Mechanism of Drug Absorption
The rate of permeation across various layers of skin tissues in the course of topical application can be expressed mathematically as
dQ / dt = Ps (Cd – Cr)
where dQ / dt = rate of permeation across various layers.
Cd = concentration of drug in the donar phase.
Cr = concentration of drug in the receptor phase.
Ps = permeability coefficient of the skin tissues.
The concentration in the systemic circulation which is penetrating in the form of pharmacological active form such as :
Ps = KcDs / hs
where Kc = partition coefficient of the penetrant molecules.
hs = overall thickness of the skin tissues.
Ds = apparent diffusivity for the steady state diffusion of penetrate moles.
If Cd >>> Cr than the equation is written as
dq / dt = PsCd
Physiological factors in percutaneous absorption
1. Skin integrity
4. Anatomic location
Formulation factors in percutaneous absorption
2. Drug concentration
6. Penetration enhancer
Methods Of Preparation
- Fusion method
- Cold method
- Dispersion method
The skin is a barrier to topically administered drugs. Although the outer layer also provide resistance to the global permeation process, invitro experiment have shown that the stratum corneum, with 10 – 15 micrometer thickness is the principal barrier. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for topical administration. The permeation of drugs through skin can be enhanced by physical methods such as mechanical disruption, electrical disruption, chemical modification and by chemical penetration enhancers e.g. sulphoxides ( dimethyl sulphoxides), pyrrolidone, alcohols, glycols, surfactants and terpenes. These compounds increase skin permeability by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle.
Skin irritation studies
Measurement of pH :
The pH of various gel formulations was determined by using digital pH meter. One gram of gel was dissolved in 100 ml distilled water and stored for two hours. The measurement of pH of each formulation was done in triplicate and average values are calculated.
Drug content :
1 g of the prepared gel was mixed with 100ml of suitable solvent. Aliquots of different concentration were prepared by suitable dilutions after filtering the stock solution and absorbance was measured. Drug content was calculated using the equation, which was obtained by linear regression analysis of calibration curve.
Viscosity study :
The measurement of viscosity of the prepared gel was done with a Brookfield Viscometer. The gels were rotated at 0.3, 0.6 and 1.5 rotations per minute. At each speed, the corresponding dial reading was noted. The viscosity of the gel was obtained by multiplication of the dial reading with factor given in the Brookefield Viscometer catalogues.
One of the crieteria for a gel to meet the ideal quantities is that it should possess good spreadability. It is the term expressed to denote the extent of area to which gel readily spreads on application to skin or affected part. The therapeutic efficacy of a formulation also depends upon its spreading value.
Spreadability is expressed in terms of time in seconds taken by two slides to slip off from gel and placed in between the slides under the direction of certain load.lesser the time taken for separation of two slides, better the spreadability. It is calculated by using the formula:
S = M . L / T
Where M = wt. tied to upper slide
L = length of glass slides
T = time taken to separate the slides
Extrudability study :
The formulations were filled in the collapsible tubes after the gels were set in the container. The extrudability of the formulation was determined in terms of weight in grams required to extrude a 0.5 cm. ribbon of gel in 10 second.
Skin irritation study :
Guinea pigs (400-500 g) of either sex were used for testing of skin irritation. The animals were maintained on standard animal feed and had free access to water. The animals were kept under standard conditions. Hair was shaved from back of guinea pigs and area of
4 cm.2 was marked on both the sides, one side served as control while the other side was test. 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, was graded as 0, 1, 2, 3 for no reaction, slight patchy erythema, slight but cofluent or moderate but patchy erythema and severe erythema with or without edema, respectively.
In vitroDiffusion studies :
The diffusion studies of the prepared gels can be carry out in Franz diffusion cell for studying the dissolution release of gels through a cellophane membrane. Gel sample (0.5g) was taken in cellophane membrane and the diffusion studies were carried out at 37 ± 1° using 250 ml of phosphate buffer (pH 7.4) as the dissolution medium. Five milliliters of each sample was withdrawn periodically at 1, 2, 3, 4, 5, 6, 7 and 8 h and each sample was replaced with equal volume of fresh dissolution medium. Then the samples were analyzed for the drug content by using phosphate buffer as blank.
In vivo studies :
Inhibition of carrageenan – induced rat paw odema – Three groups of 6 male wistar albino rats were used one for marketed sample (reference). Other for test formulation and one group for control. The volume of unilateral hind paw test animal were measured. On each paw, 100 mg of preparation was carefully rubbed twice at 1 and 2 h. before carrageenan administration. They were placed in cages with copography meshes. 0.1 ml of 1 % w/v carrageenan was injected subcutaneously into the paw and volume of hind paw measured at hourly interval for 5 h. using a mercury plethysmometer. Percentage of inhibition was calculated.
The stability studies were carried out for all the gel formulation by freeze - thaw cycling. In this syneresis was observed by subjecting the product to a temperature of 4° C for 1 month, then at 25°C for 1 month , then at 40°C for 1 month. After this gel is exposed to ambient room temperature and liquid exudates separating is noted.
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Ms. Rashmi is a M.Pharm. Final year student of ASBASJSM College of Pharmacy, Bela, Ropar, India. She had completed his graduation from SBSPGI, Balawala, Dehradun. She has very good academic and extra circular record.
Mr. Rajeev Garg is working a lecturer cum research scholar in department of pharmaceutics in ASBASJSM College of Pharmacy, Bela, Ropar, India. He had completed his graduation from Rameesh institutions, Greater Noida and post graduation from B.N.College of pharmacy, Udaipur, Raj.
Mr. Sandeep Kumar is working as Assistant professor in department of pharmaceutics in ASBASJSM College of Pharmacy, Bela, Ropar, India.
Dr. G. D.Gupta is a Director and Principal in ASBASJSM College of Pharmacy, Bela, Ropar, India>. Dr. Gupta has author of number of books and published more than 100 Research Paper / Abstract in National and International conferences.
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Topical delivery system refers to application of a drug on the surface of the skin to deliver the drug to the skin to treat dermal disorders. Transdermal systems, on the other hand, deliver the drug through the skin to the general circulation for systemic effects. These systems follow absorption of active ingredients through the transdermal barriers especially through stratum corneum by various mechanisms for localized effects in dermis and epidermis or absorption through the blood capillaries present in these layers for systemic effects.
Absorption of active ingredients through various body sites depends on various factors like permeability of skin, rate of blood flow and age. Transdermal systems have various advantages over other systems; it provides sustained release of drug, and can be applied when patient is suffering from nausea, vomiting, diarrhea etc. or if patient is unconscious, also gastrointestinal irritation can be avoided. Different types of transdermal systems are available as single layer, multiple layer, reservoir type, matrix type and vapour patch systems. The first transdermal system Transderm Scop was approved by USFDA in 1979 for the drug scopolamine. Since then there have been many advances in the Transdermal and Topical Delivery Systems.
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