About Authors:
Arpana Kumari*, Saurabh SS, Poonam K, Rathore KS1
*Department of Pharmaceutics, Lachoo Memorial College of Science and Technology, Pharmacy Wing,
Jodhpur, 342001 (Raj) India.
1BN Institute of Pharmaceutical Sciences, Udaipur-313002 (Raj.)
111arpnasingh@gmail.com
Abstract:
A unique aspect of dermatological pharmacology is the direct accessibility of the skin as a target organ for diagnosis and treatment. When gel and emulsion are used in combined form they are referred as Emulgel. Among the various groups of semisolid preparations, the use of gels has expanded both in cosmetics and in pharmaceutical preparations. Despite of several advantages of gels there is a limitation in delivery of hydrophobic drug moiety. This limitation can be overcome by the use of novel topical drug delivery i.e. emulgel. The major objective behind emulgel is delivery of hydrophobic drugs via skin. Emulgels show dual release control system i.e. gel and emulsion. 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 system as well as on conventional systems in various aspects. Emulgels have several favourable properties for dermatological use such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, nonstaining, long shelf life, bio-friendly, transparent and pleasing appearance. So emulgels can be used as better topical drug delivery systems over present systems. The use of emulgels can be expanded in analgesics, anti-inflammatory, anti-fungal, anti-acne drugs and various cosmetic formulations.
Reference Id: PHARMATUTOR-ART-1991
INTRODUCTION
Topical preparations are used for the localized effect at the site of their application by virtue of drug penetration into the underlying layer of skin or mucous membrane1. Topical drug delivery (TDD) can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorders with the intent of containing the pharmacological or other effect of the drug to the surface of skin or within. A unique property of dermatological pharmacology is the direct accessibility of the skin as a target organ for diagnosis and treatment2. Topical preparation pertain to medicaments applied to the surface of a part of the body and is a term used to describe formulations that have effects only in a specific area of the body and are formulated in such a manner that the systemic absorption of the medicament is minimal3. TDD has several advantages over conventional routes4,5. It avoids the first pass metabolism and the gastrointestinal tract. It has the potential for sustained as well as controlled drug release. Moreover, it is a noninvasive mode of drug delivery with no trauma or risk of infection6. The most common example of topical dosage forms include solutions, suspensions, emulsions, semisolids, and sprays7. Gels are a relatively newer class of dosage form created by entrapment of large amount of aqueous or hydroalcoholic liquid in a network of colloidal solid particles. In spite of many advantages offered by gels a major limitation is in the delivery of hydrophobic drugs. So to overcome this drawback an emulgel based approach has been appreciated which is the combination of emulsion and gel8. In 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 allow 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. The presence of a gelling agent in the water phase converts a classical emulsion into an emulgel9. Emulgels for dermatological use have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, nonstaining, long shelf life, biofriendly, transparent and pleasing appearance.
Drug delivery across the skin10:
The epidermis is the most superficial layer of the skin and is composed of stratified keratinized squamous epithelium which varies in thickness in different parts of the body. Blood vessels are distributed profusely beneath the skin. The skin acts as a two way barrier to prevent absorption or loss of water and electrolytes. There are three primary mechanisms of topical drug absorption: transcellular, intercellular, and follicular. Most drugs pass through the torturous path around corneocytes and through the lipid bilayer to viable layers of the skin. The barrier resides in the outermost layer of the epidermis, the stratum corneum. To overcome this problem various penetration enhances are used to improve the drug absorption through stratum corneum.
Advantages of Using Emulgels as a Drug Delivery system10:
1) Hydrophobic drugs can be easily incorporated into gels.
2) It shows better stability.
3) It has better loading capacity.
4) Production feasibility and low preparation cost.
5) No need of intensive sonication.
6) Controlled release.
MATERIALS AND METHODS
Additives/Excipients used in Emulgel Formulation10:
1) They must be non-toxic.
2) They must be commercially available in applicable grade.
3) Their cost must be acceptably cheap.
4) They must not be contraindicated.
5) They must be physically and chemically stable by themselves and in combination with drugs and other components.
6) They must be color compatible.
a. Aqueous Materials and oils:
This forms the aqueous phase of the emusion. Commonly used agents are water and alcohols.Oil forms the oily phase of the emulsion. Mostly used oils in oral preparations are non-biodegradable mineral and castor oils and various fixed oils of vegetable origin(e.g. arachis, cottonseed, and maize oils). The examples of oil are given in Table no.1.
b. Emulsifiers:
Emulsifying agents are used both to promote emulsification at the time of manufacture ant to control stability during a shelf life for commercial preparations e.g. Polyethylene glycol 40 stearate, Sorbitan mono-oleate, Polyoxyethylene sorbitan mono-oleate, Stearic acid and Sodium stearate.
c. Gelling Agent:
These are used to increase the consistency of any dosage form. They can also be used as thickening agent e.g. Carbopol 934P, Carbopol 940, Sodium carboxy methyl cellulose, Hydroxy propyl methyl cellulose.The examples of gelling agents are given in Table No. 2
d. Permeation Enhancers:
These are the agents that partition into and interact with skin constituents to induce a temporary and reversible increase in skin permeability. Some of these materials are given in table No. 3.
METHOD OF PREPARATION11:
Step 1: Formulation of Emulsion either O/W or W/O
Step 2: Formulation of gel base
Step 3: Incorporation of emulsion into gel base with continuous stirring.
The gel in formulations are prepared by dispersing Carbopol 934 and Carbopol 940 in purified water with constant stirring at moderate speed. Then the pH of the Gel is adjusted to 6 to 6.5 using triethanolamine (TEA). The oil phase of the emulsion is prepared by dissolving Span 20 in light liquid paraffin while the aqueous phase is prepared by dissolving Tween 20 in purified water. Methyl and Propyl paraben is dissolved in Propylene glycol whereas drug is dissolved in ethanol and both solution is mixed with aqueous phase. Both the oily and aqueous phase were separately heated to 70 to 80oC; then the oil phase is added to aqueous phase with continuous stirring until cooled to room temperature. The gel and emulsion is mixed in a ratio of 1:1. Add glutaraldehyde in during of mixing of gel and emulsion.
EVALUATION PARAMETERS12:
1. Physical appearance: The prepared emulgel formulations are inspected visually for their color, homogeneity, consistency and phase separation.
2.Rheological study: The viscosity of the different emulgel formulations is determined at 25oC using a cone and plate viscometer with spindle 52 and connected to a thermostatically controlled circulating water bath.
3. Spreadibility: Spreadibility is determined by apparatus suggested by Multimer et al (1956) which is suitably modified in the laboratory and used for the study. It consists of a wodden block, which is provided by a pulley at one end. By this method the Spreadibility is measured on the basis of Slip and Drag characteristic of emulgel. A ground slide is on this block. An excess of emulgel (2g) under study is placed on this ground slide. The emulgel is sandwiched between this slide and another glass slide hving the dimension of fixed ground slide and provided with the hook. A 1kg 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 gm. With the help of string attached to the hook and the time (in seconds) required by the top slide rto cover a distance of 7.5 cm be noted. A shorter interval indicates better Spreadibility.
4. Skin irritation study: The preparation is applied on the properly shaven skin of rat and its adverse like change in color, change in skin morphology should be checked up to 24 hours. The total set of 8 rats can be used of the study. If no irritation is occurred then test is passed. If the skin irritation symptom occurs in more than 2 rats the study should be repeated.
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5. In Vitro Permeation study: In vitro release study is carried out using Franz diffusion cell.
a) Equation used to determine drug release:
i) Higuchi’s equation: Q=k2t
Where- Q- Percent of drug release at time t
K2- Diffusion rate constant
ii) Zero-order equation: Q= k0t
where – Q- Amount of drug released at time t
k0- zero order drug release.
iii) First-order equation: ln (100-Q)= ln 100-k1t
where – Q -Percent of drug release at time t
k1-The first order release rate constant.
6.Extrudability study of topical Emulgel (Tube Test):It is a usual empirical test to measure the force required to extrude the material from tube. It is based upon the determination of weight required to extrude .5 cm ribbon of Emulgel in 10 sec from lacquered collapsible aluminium tube. The test is performed in triplicate and the average value is calculated.
Extrudability=Weight applied to extrude Emulgel from tube (in gm) / Area (in cm2)
7. Swelling Index: To determine swelling index of prepared emulgel, 1 gm of gel is taken on porous aluminium foil and then placed separately in a 50 ml beaker containing 10 ml .1 N NaOH. Then samples were removed from beaker at different time intervals and put it on dry place for sometime after it reweighed.
Swelling index (SW) % = (Wt-Wo) / Wo ×100.
Where , (SW)% = Equilibrium percent swelling, Wt= Weight of swollen emulgel after time t, Wo = Weight of original emulgel at zero time.
8. Measurement of pH: it is determined with the help of Digital pH meter. One gm of gel is dissolved in 100 ml of distilled water and placed for two hours. The measurement of pH of each formulation is done in triplicate and average value is calculated.
9. Stability studies: The prepared emulgels are packed in aluminium tube(5g) and subjected to stability study at 5oC, 25oC ?60% RH, 30oC / 65% RH, and 40oC / 75% RH for a period of 3 months. Samples are withdrawan at 15 day time intervals and evaluated at physical appearance, pH, rheological properties, drug content and drug release profile.
10.Drug Content Determination: Take 1 gm of emulgel. Mix it in suitable solvent.Filter it to obtain clear solution. Determine its absorbance using spectrophotometer. Standard plot of drug is prepared in same solvent. Concentration and drug content can be determined by using the same standard plot by putting the value of absorbance in the standard plot equation:
Drug content = ( Concentration × Dilution factor × Volume taken) × Conversion factor.
Table No.1 Use of oils
|
CHEMICALS |
QUANTITY |
DOSAGE FORM |
|
Light liquid paraffin |
7.5% |
Emulgel |
|
Isopropyl palmitate |
7-7.5% |
Emulsion |
|
Isopropyl palmitate |
7-7.5% |
Emulsion |
|
Isopropyl stearate |
7-7.5% |
Emulsion |
Table No.2 Use of different gelling agent
|
GELLING AGENT |
QUANTITY |
DOSAGE FORM |
|
HPMC 2910 |
2-2.5% |
Emulgel |
|
HPMC |
3.5% |
Gel |
|
Sodium C.M.C. |
1% |
Gel |
|
Carbopol 934 |
1% |
Emulgel |
|
Carbopol 940 |
1% |
Emulgel |
Table No. 3 Use of different penetration enhancers
|
PENETRATION ENHANCERS |
QUANTITY |
DOSAGE FORMS |
|
Oleic acid |
1%% |
Gel |
|
Lecithin |
5% |
Gel |
|
Urea |
10% |
Gel |
|
Eucalyptus oil |
NA |
None |
|
Isopropyl myritate |
5% |
Gel |
|
|
4-6% |
Emulgel |
CONCLUSION
Emulgel is the recent technique for the delivery of hydrophobic drugs and obviously it is a very good technique for drug delivery of combination of both hydrophilic and hydrophobic drugs. In the coming years the topical drug delivery will be used extensively to impart better patient compliance. Since emulgel is helpful in enhancing Spreadibility, adhesion, viscosity and extrusion, it is going to become a popular delivery system for topical application in future.
ACKNOWLEDGEMENT:
I am very thankful to the teachers of Lachoo Memorial college of Science and Technology for supporting me at each and every step of my work.
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10. Bhatt Preeti et al. Emulgels: A Novel Formulation Approach for Topical Delivery of Hydrophobic Drugs. International Research Journal of Pharmacy 2013; 4(2):12-15.
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12. Joshi Baibhav et al. Emulgel: A Comprehensive Review on the Recent Advances In Topical Drug Delivery. International Research journal of Pharmacy 2011; 2(11): 66-70.
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