INTRODUCTION:

Topical drug delivery systems are such system in which direct application of a formulation containing an active pharmaceutical ingredient to the skin to obtain the localizing effect of drug.¹Topical drug delivery system has many advantages such as the ability to deliver drug more selectively to the specific site and prevention of incompatibility associated with gastro-intestinal region.² Moreover, topical delivery of the drug by avoiding first pass metabolism provides an increased bioavailability and consistent delivery for an extended period.³In topical drug delivery system, drug reaches to the target site via diffusion and their absorption takes place through the skin.Percutaneous absorption can be improved by increasing the release rate of the drug from dosage form.⁴The release rates of medications from topical preparations depend straight forwardly on various physical, chemical properties of the carrier and the medication utilized.Since the mid-1980s, emulgel have been picking up significance in pharmaceutical topical semisolid dosage forms.

Emulgel:

Emulgel are emulsions, either of the water-in-oil or oil-in-water type, which are gelled by mixing with a gelling agent.⁵ The emulsion acts as controlled release drug delivery system in which the drug particles are entrapped in internal phase and go through the external phase to the skin and gets absorbed slowly. The drug reaches to the external phase of the skin in a controlled manner through the internal phase which act as a reservoir of the drug. Gel captures small drug particles and provides its release in a controlled manner because of a crosslinked network. It increases the contact period of medication over the skin because of its mucoadhesive property.⁶Since Emulgel possesses the property of both gel and emulsions it acts as dual control release system.⁷

Gels that are used for dermatological property have a few positive properties, for example, being emollient^8,9, greaseless, thixotropic, easily removable, non-staining and compatible with various excipients. Release rate, and stability of incorporated drug, can be affected by the type and concentration of polymer which forms the gel. Emulgel may serve as a better option when it is concerned with the topical delivery of poorly water soluble drug. It is proven better and a stable vehicle for poorly water -soluble or hydrophobic drugs.¹⁰

Figure 1: Emulgel structure

Advantages of emulgel:¹¹

· Incorporation of hydrophobic drugs.

· Better loading capacity and better stability.

· Controlled release.

· Avoiding first pass metabolism.

· More selective for a specific site.

· Improved patient compliance and suitability for self medication.

Disadvantages of emulgel:¹²

· Skin irritation on contact dermatitis.

· Possibility of allergenic reactions.

· Larger particle size drugs are not easy to absorb through the skin.

· The occurrence of the bubble during formulation of emulgel.

Materials required for formulation of emulgel:

i. Aqueous material¹³

ii. Oils¹⁴

iii. Emulsifiers¹⁵

iv. Gelling agent¹⁶

v. Permeation enhancers¹⁷

Method of Preparation:

Step1: Preparation of gel using the gelling agent

Step 2: Preparation of emulsion

Step 3: Addition of the emulsion into gel base

Finally emulsion was added in gel base to form emulgel.¹⁸

Figure 2: Schematic procedure of emulgel preparation

Characterization of emulgel:

i. Physical appearance:

The prepared emulgel is inspected for the colour, homogeneity, consistency.¹⁹

ii. pH:

The pH values of 1% aqueous solutions of the prepared gels were measured by a digital pH meter. Electrodes were completely dipped into the semisolid formulations and pH was noted.²⁰

iii. Spreadability:

Two glass slides of 6x2cm each were selected. The formulation was kept over one of the slides whose spreadability had to be determined (500mg). This slide was placed over the other slide in such a way that formulation was sandwiched between the two slides. The formulation between the two slides was squeezed consistently to frame a slight layer, for this reason, weight (100g) was set upon the upper slide. The excess of the formulation adhering to the slides was scrapped off after the weight was removed. The lower slide was fixed on the surface of the apparatus and the upper slide was tied to a string. To this sting load (20g) could be applied with the help of a simple pulley. Under the direction of weight applied the time taken for the upper slide to move the distance i.e of 6cm and separate away from the other slide (lower) was noted. The experiment was repeated (n=3) and the average of such determinations was calculated for each formulation

Spreadability =

Where,

M = Weight which is tied to the upper slide (20gm),

L = Length taken of glass slide (6cm)

T = Time taken (seconds). The delivery of the correct dose of the drug depends highly on the spreadability of the formulation.²¹

iv. Swelling index:

One g of the gel is taken on porous aluminum foil and then kept separately in a beaker of 50 ml having 10 ml 0.1 N NaOH. Then samples were taken from beakers at different time points and put it on a dry place for some time after it reweighed. Swelling index is calculated as follows:

Swelling index (SW %) = [(w_t– w_o) / w_o x 100]

Where,

Wt = Weight of swollen emulgel after time t, Wo = Initial weight of emulgel at zero time

(SW) % = Percent swelling Index²²

v. Extrudability study of topical emulgel (Tube Test):

It is a typical experimental test to measure the force required to expel the material from the tube. The formulation, whose extrudability was determined, filled in clean, lacquered aluminum collapsible metal tubes. The tubes were pressed by the help of finger to extrude the material. In the recent study, the method adopted for evaluating emulgel formulation for extrudability is based upon the amount in the percentage of emulgel. Emulgel taken from lacquered aluminum collapsible tube on the application of weight in grams required to extrude at least 0.5 cm ribbon of emulgel in 10 seconds.²³ The experiment was repeated (n=3) and the average of such determined value was calculated for each formulation:

weight applied to extrude emulgel form tube (gm)

Extrudability = --------------------------------------------------------

Area (cm²)

vii. Drug content determination:

Gel formulation (1 g) was dissolved in suitable solvent and filtered. The resulting solution absorbance was noted using UV-Visible spectrophotometer. Drug content was determined from calibration curve for drug.²⁴

Drug Content = (Concentration × Dilution Factor × Volume taken) × Conversion Factor.

viii. Rheological studies:

The rheological properties of emulgel samples are determined using cone and plate Brookfield viscometer. About 0.5g of the formula to be tested is applied to the plate and left for equilibrium, measurements are made at 20°C and at shear rates ranging from 0.4 to 400/second corresponding to 0.2 to 200rpm with 10 seconds between each two successive speeds and then in a descending order. The hysteresis loop between the upward and downward curve is studied. The flow index is determined by linear regression of the logarithmic form:

σ= kⁿ

Where σ is the shear stress, γ is the shear rate, k is the consistency index, and n is the flow index. n =1 when the flow is Newtonian, if n >1 or n<1 indicates shear thickening or shear thinning respectively.²⁵

ix. Skin irritation Study:

The skin irritation test is carried out on male Wistar albino rats weighing 200 to 225g. The animals are kept under standard laboratory conditions, with temperature of 25±1°C and relative humidity of 55 ±5%. The animals are housed in polypropylene cages, six per cage, with free access to standard laboratory diet and water. The hair on the dorsal side of the rats is removed with an electric hair clipper on the previous day of the experiment. The rats are divided into three groups (n =6). The animals are applied with new napping gel, or new formalin solution, each day up to 6 days. Finally, the application sites are graded according to a visual scoring scale, always by the same investigator.²⁶

x. In vitro drug release study:

Franz diffusion cell (with effective diffusion area 3.14cm² and 15.5ml cell volume) is used for the drug release studies. Emulgel (200mg) is applied on to the surface of egg membrane. The egg membrane is clamped between donor and receptor chamber of diffusion cell. The receptor chamber is filled with freshly prepared phosphate butter (pH 5.5) solution to solubilize the drug. The receptor chamber is stirred by magnetic stirrer. The samples are collected at suitable time interval, sample are analyzed for drug content by UV-visible spectrophotometer after appropriate dilutions.²⁷

xi. Stability studies:

The optimized emulgel formulation was selected for stability study. Sufficient quantity of emulgel formulation was sealed in 10 gm collapsible tube in triplicate, and subjected to stability studies at 5°C, 25°C, /60% RH, 30°C 65%RH and 40°C/ 75%RH for a period of 3 months.²⁸

APPLICATIONS:

Examples of marketed emulgel formulations with their pharmaceutical application are given in Table 1.

Table 1: Marketed emulgel formulations^29,
30

Drug Name	Brand Name	Category	Company
Diclofenac diethyl ammonium	Voltarol 1.16% emulgel	Anti-inflammatory	Novartis
Diclofenac sodium	Diclomax emulgel	Anti-inflammatory	Torent Pharma
Miconazole nitrate, Hydrocortisone	Miconaz-H-emulgel	Topical corticosteroid and antifungal	Medical Union Pharmaceuticals
Clindamycin phosphate	Denacine emulgel	Anti-acne	Beit jala pharmaceutical company
Diclofenac potassium	Cataflam emulgel	Anti-inflammatory	Novartis
Diclofenac diethylamine	Diclon emulgel	Anti-inflammatory	Med Pharma
Metronidazole	Lupigyl gel	Antibiotic	Lupin Pharma
Clindamycin, Adapalene	Excex gel	Antibiotic and Anti-acne	Zee Laboratories
Benzoyl peroxide	Pernox gel	Anti-acne	Cosme Remedies Ltd
Clobetasol propionate	Topinate gel	Corticosteroid	Systopic Pharma
Tezarotene	Zorotene gel	Anti-acne	Elder Pharmaceuticals
Nadifloxacin	Nadicin cream	Anti-acne	Psychoremedies
Azithromycin	Avindo gel	Antibiotic	Cosme Pharma Laboratories
Clindamycin phosphate Allantoin	Clina gel	Anti-acne	Stiefel Pharma
Clotrimazole, Beclomethasone dipropionate, Neomycin	Cloben gel	Antifungal , corticosteroid and Antibiotic	Indoco Remedies

CONCLUSION:

Emulgel is used as the recent technique among the topical drug delivery systems. It is mainly used for the delivery of both hydrophobic and hydrophilic drug. Emulgel technique contains both oil and aqueous (i.e. gel base) base so it can be used for hydrophobic drugs. Since emulgel shows enhanced spreadability, adhesion, viscosity and extrusion. This novel drug delivery becomes a popular formulation.

FUTURE PROSPECTIVES:

As compared to other topical delivery systems, gel provides an aqueous environment to the drug and favours its dissolution and provides quicker release of drug. All such advantages of emulgel over other topical delivery systems make them more superior in drug delivery. In future, these properties will be used to formulate more number of topical drugs in the form of emulgel.

ACKNOWLEDGEMENT:

We express our sincere thanks to Dr. L. Rathaiah, Chairman, Vignan Group of Institutions for providing necessary facilities to carry out the above review.

REFERENCES:

1. Zignani M, Tabatabay C, Gurny R. Topical Semi-solid drug delivery: kinetics and tolerance of ophthalmic hydrogels. Advanced Drug Delivery Reviews. 1995; 16: 51-60.

2. Kikwai L, Babu RJ, Prado R, Kolot A, Armstrong CA, Ansel JC, Singh M. In vitro and in vivo evaluation of topical formulations of spantide II. AAPS Pharmaceutical Science and Technology. 2005; 6: 565-572.

3. Moshfeghi AA, Peyman GA: Micro- and nanoparticulates. Advanced Drug Delivery Reviews.2005; 57: 2047–2052.

4. Shokri J, Azarmi S, Fasihi Z. Effect of various penetration enhancers on percutaneous absorption of piroxicam from emulgel. Research in Pharmaceutical Sciences. 2012; 7: 225-2234.

5. Mohamed MI. Optimization of chlorphenesin emulgel formulation. AAPS Journal. 2004.

6. Alexander A, Ajazuddin, Tripathi DK, Vrema ST, Maurya J, Patel S. Mechanism responsible for mucoadhesion of mucoadhesive drug delivery system: a review. International Journal of Applied Biology and Pharmaceutical Technology.2011; 2: 434–445.

7. Jain A, Deveda P, Vyas N, Chauhan J. Development of antifungal emulsion based gel for topical fungal infection. The International Journal of Periodontics and Restorative Dentistry. 2011; 2: 18-25.

8. Panwar AS, Upadhyay N, Bairagi M, Gujar S, Darwhekar GN, Jain DK. Emulgel: a review, Asian Journal Of Pharmacy & Life Science.2011;1: 2231-2243.

9. Sarisozen C, Vural I, Levchenko T, Hincal AA, Torchilin VP. PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells. Drug Delivery.2012; 19: 169-176.

10. Dickinson E. Hydrocolloids as emulsifiers and emulsion stabilizers. Food Hydrocolloids 2009; 23: 1473-1482.

11. Jain NK, Progress in controlled and novel drug delivery systems. New Delhi: CBS publishers and distributors, 2004; 1: 319-20.

12. Hardenia A, Jayronia S, Jain S. Emulgel: An emergent tool in topical drug delivery. International Journal of Pharmaceutical Science and Research. 2014; 5: 1653-1660.

13. Lachman, L.; Lieberman, H.A. The Theory and Practice of Industrial Pharmacy. 3rd Ed. Varghese Publishing house; 1990; 534.

14. Vyas, S.P.; Khar, R.K. Controlled Drug Delivery. 1st Ed. Vallabh Prakashan; 2002; 416-417.

15. Curr AEB. Transdermal Drug Delivery: Penetration Enhancement Techniques Heather. Drug Delivery. 2005; 2: 23-33.

16. Mortazavi SA, Aboofazeli R. An investigation into the effect of various penetration enhancers on percutaneous absorption of piroxicam. Iranian Journal of Pharmaceutical Research. 2003; 135-140.

17. Jacob SW, Francone CA. Structure and Function of Man, (2).

18. Baibhav J, Singh G, Rana A C, Saini S, Singla V. Emulgel: A comprehensive review on recent advancement on topical drug delivery. International Research Journal of Pharmacy 2011; 2(11): 66-70.

19. Prajapati MN, Patel MR, Patel KR, Patel NM. Emulgels: a novel approach to topical drug delivery. International Journal of Universal Pharmacy and Bio sciences. 2013; 2(1): 134-148.

20. Panwar AS, Upadhyay N, Bairagi M, Gujar S, Darwhekar GN, Jain DK. Emulgel: A review. Asian Journal of Pharmacy and Life Sciences. 2011; 1(3): 333-343.

21. Garg A, Aggarwal D, Garg S, and Singla AK. (2002). Spreading of Semisolid Formulations: An Update. Pharmaceutical Technology. Circle/eINFO 74.

22. Khalil YI, Khasraghi AH, Mohammed EJ. Preparation and evaluation of physical and, rheological properties of clotrimazole emulgel. Iraqi Journal of Pharmaceutical Sciences. 2011; 20(2): 1927.

23. Baibhav J, Singh G, Rana A. C, Saini Seema, Singla Vikas,: Emulgel: A comprehensive review on the recent advances in topical drug delivery, International Research Journal of Pharmacy.2011; 2(11): 66-70.

24. Singla V, Saini S, Joshi B, Rana AC. Emulgel: A new platform for topical drug delivery. International Journal of Pharma and Bio Sciences. 2010; 3(1):21-29.

25. Nahla Salah Barakat. Evaluation of glycofurol-based gel as a new vehicle for topical application of naproxen. AAPS Pharmaceutical Science and Technology. 2010;11(3): 1138-1146.

26. Ranga Priya M, Sellakumar V, Natarajan R, Mohan Kumar K. Formulation and In-Vitro evaluation of ciprofloxacin loaded topical emulgel. International Journal of Pharmaceutical and Chemical Sciences. 2012; 1: 237-242.

27. Joshi Baibhav, Singh Gurpreet, Rana AC, Saini Seema. Development and characterization of clarithromycin emulgel for topical delivery. International Journal of Drug Development & Research. 2012; 4: 310-323.

28. ICH Harmonized Tripartite Guidelines, Stability Testing of New Drug Substances and Products. ICH Committee 2.

29. Abhijeet Ojha, Mini Ojha, Satheesh Madhav NV. Recent advancement in emulgel: A novel approach for topical drug delivery. International Journal of Advances in Pharmaceutics. 2017; 06(01): 17-23.

30. Davinder Kumar, Jasbir Singh, Mamta Antil and Virender Kumar. Emulgel-Novel topical drug delivery system–Acomprehensive review. International Journal of Pharmaceutical Sciences and Research. 2016; 7(12): 4733-4742.

Received on 06.05.2020 Modified on 19.06.2020

Research J. Pharm. and Tech. 2021; 14(5):2903-2906.

DOI: 10.52711/0974-360X.2021.00509