INTRODUCTION:

The use of a medication-containing formulation applied over the skin to cure a cutaneous illness is referred as topical drug delivery system.¹ For systemic and local treatment, topical medication delivery is the best option. This system is typically used when other drug administration routes such as oral, rectal, sublingual, and parental fail to cure a local infection on skin like a fungal infection.²The main benefit of this route is that it avoids the first-pass metabolism, GIT irritation, and metabolic degradation that come with oral administration. Only 25-45 percent of the orally supplied dose reaches the blood circulation due to presystemic metabolism. Gel compositions have been suggested as a topical treatment to overcome these drawbacks.³

Merits of Topical Drug Delivery Systems:⁴

· Avoid the first pass metabolism.

· Easy to apply.

· Avoidthe risks and disruption of intravenous medication.

· Easily termination of medication.

· Deliver drugto a site of drug action.

· Avoidance of both stomach and intestinal incompatibility.

· The patient compliance will improve.

· The self-medication is possible.

Demerits of Topical Drug Delivery Systems:⁵

· Causes irritation to the skin.

· Some drugs having poor permeability through the skin are not easily administered.

· The drugs having largeparticle size are not easily absorb through the skin.

Factors Affecting Topical Absorption of Drug:^6,7

Physiochemical factors associated to drug and physiological factors related to patient that affect the permeation of drug through stratum corneum are listed below:

Physiological Factors:

1. Skin thickness and pH

2. Lipid content.

3. Hair follicles density.

4. Sweat glands density.

5. Blood flow.

6. Hydration of skin.

7. Skin inflammation.

Physiochemical Factors:

1. Partition coefficient.

2. Molecular weight (< 400 Dalton).

3. Ionization yield.

4. Effect of vehicles.

Emulgel:

An emulgel is manufactured by mixing the emulsion and gel. Most of the drugs can be deliver through the skin by using o/w and w/o type of emulsion as a vehicle. The emulgel is simple prepared by mixing gelling agent in water phase with the emulsion. In recent years, different types of polymers having both the properties i.e. thickener and emulsifier are used to formulate stable emulgel.⁸

Parts of Emulgel:

Emulsion.

Gel.

Emulsion:

The emulsions are biphasic systems in which two unmixable liquids made mixable by using emulsifying agent. Emulsion is of mainly two types o/w or w/o. The drug can be delivered by using emulsion as a vehicle. The emulsifiers are used to stabilized the emulsion. They can be easily washed off from skin and have good penetration capability.

Gel:

A gel is one which having properties between solid and liquids. A gel is mainly consistingof a polymer. This polymer get swells in water and make a transparent gel. The amount of liquid which entraps within the gel is measured as rigidity of the gel. Thegelhastexture like a solid material. These are effective to undergoing large alteration in their physical state i.e. from solid to liquid.

Types of emulgels:³

Macro emulsion gel:

Macroemulgel are the most ordinary type of emulgels. The emulsion having droplet size of more than 400nm. Macro emulsions are thermodynamically unstable. They canstabilize by using surfactants. Macroemulsions are visually opaque. The individual droplet of emulsion can be readily observed under the microscope.

Micro Emulsion gel:

Micro emulsions are transparent and thermodynamically stable as their droplet size range from 10 to 100nm. Coalescence is not observed in microemulsion. Microemulsion is multi-component systemcomprising of non-polar, aq, surfactant and co-surfactant components.

Nanoemulgel:

The nanoemulgel is prepared by incorporating the nanoemulsion into gel base. These are thermodynamically stable. Generally, nanoemulgel is dispersion of oil and water. These are stabilized by addition of surfactant along with co-surfactant molecule which reduces the force of attraction between the molecules at the interface of two fluids. The size of droplets in nanoemulsion is less than 100nm.

Constituents of emulgel:

Vehicle:⁹

The vehicle has following properties:

· Deposit the drug effectively on the skin to produce even film.

· The drug is released from the vehicle so it can reach at the active site.

· Site specific drug delivery.

· Maintain the therapeutic level of drug in target tissue for sufficient time period.

Aqueous material:¹⁰

The aqueous phase of emulsion is prepared from the aq. material. The most probably used agents are water and Alcohols.

Oils:^11,¹²

The oils are utilized as vehicle for drug or for their sensory characteristics. For topical preparations oils are used by oneself or in combination with paraffins. For oral preparations non-biodegradable minerals, various fixed oils, essential oils are utilized as oil phase. Oils provides both laxative effect and as a nutritional supplement. Some e.g. of oils used in emulgel are castor oil, maize oil, arachis oil, lemongrass oil, etc.

Table 1: Different oils used in emulgels

Oil	Dosage Form	Comment	References
Isopropyl myristate	Microemulsion	IPM was screened as to a good solubilizing capacity of the microemulsion system	8
Isopropyl palmitate	Emulsion	isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. It was observed that emulgel formu- lations prepared with isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. It was observed that emulgel formu- lations prepared with isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. It was observed that emulgel formu- lations prepared with isopropyl palmitate showed better drug release as compared to those prepared with liquid paraffin. Better drug release from isopropyl palmitate than liquid paraffin emulgel	9
Light liquid paraffin	Emulsion	Shows better release in high concentration	10
Clove oil	Nanoemulsion	clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.	11

Emulsifiers:¹³

These are the agents used to provide emulsification and maintain the stability of emulsion during shelf life. These are of either cationic, anionic and non-ionic. Mainly non-ionic surfactants are used as emulsifiers in emulsion. Commonly used non-ionic surfactants are Tween 80, Span 80, Span 20, Tween 20, stearic acid, and sodium stearate.

Gelling agents:¹⁴

Mainly used to upgrade the consistency of dosage form. Most commonly used gelling polymers are of different carbomer grades such as Carbopol 934, Carbopol 940, Carbopol 941 etc. Gelling polymers from natural, synthetic and semi-synthetic sources are used as gelling agents.

Natural polymers: Xanthan gum, guar gum, tragacanth, dextran.

Semi synthetic polymers: HPMC, HPC, ethyl cellulose, sodium alginate.

Synthetic polymers: Carbopol-934, Carbopol-940, poloxamers.

Cellulose polymers:

· Methylcellulose: At 1500 cps, methylcellulose (MC) is used. It produces thinner gels with a high drug resistance. It works well with water, 70% ethanol.

· Hydroxypropyl cellulose: If 15 percent or more of a distinctive dissolvable is used to separate the strong solution, hydroxypropyl cellulose is a decent gelling administrator.

· Hydroxypropyl methyl cellulose: Is a superior gelling administrator for time released definitions.

· Carboxymethylcellulose: It is utilised to deliver gel as a piece of centralizations of 4 to 6 percent medium thickness. It is incompatible with alcohol. To avoid drying, glycerine can be used.

Poloxamers:

Poloxamers are polyoxymethylene and polyoxypropylene copolymers (Pluronic’s®). They'll make thermoreversible gels in the core that extend from 15% to half of the way out. This implies that they are liquids at cool (colder) temperatures, but gels at room or body temperatures. Poloxamers are white waxy granules that, when spread in cold water/cooled to 0-10°C overnight, form a casing around transparent liquids.

Carbomers:

The term "carbomer" refers to a group of polymers known as Carbopol®. Carbopol’s® were originally introduced in the mid-1950s. They are dry powders with large mass densities and shape acidic watery courses of action as a social event (pH around 3.0). At higher pH., thicken around 5 to 6. They will also expand to 1000 times their amazing volume in a liquid game plan with that pH. The thickness of their responses ranges from 0 to 80,000cps.

Table 2: Use of gelling agent as polymer in various gel formulation¹⁴

Sr. No.	Drug	Polymer	Formulation	Comment
1	Ibuprofen	Chitosan	Gel	Study of topical and systemic effect
2	Piroxicam	Carbopol 934,940	Emulgel	Comparative study of drug release
3	Clotrimazole	Carbopol 934	Emulgel	Study of rheological properties
4	Aceclofenac	Carbopol, HPMC, Sod. CMC	Gel	Carbopol gel shows superior release
5	Mefenamic acid	Carbopol 934, HPMCK4M	Emulgel	Release study and pharmacologic action
6	Fluconazole	Carbopol- 934	Liposomal gel	Increase permeation and deposition
7	Ketoconazole	Carbopol- 934, 940	Emulgel	Comparative study of polymer and drug release
8	Nimesulide	HPMC, Carbopol940, Natural polymer	Gel	Effect of gelling agent on release
9	Chlorphenisn	Carbopol 934, HPMC	Emulgel	Effect of gelling agent on release
10	Miconazole	Carbopol-940, 934	Emulgel	Controlled delivery

Characterization of gellified emulsion:

Physical appearance:¹⁸

The prepared Emulgel isvisually inspected for their colour, homogeneityand consistency.

Determination of pH:¹⁹

The pH of prepared emulgel formulation is determine by using digital pH meter.

Measurement of Viscosity of emulgel:²⁰

The viscosity of emulgel is measured by use ofBrookfield viscometer at 25°C. For this plate and cone type of viscometer with spindle no 52 is used. The emulgel formulation is weighted about 0.5gm set is shut and plate. The spindle is allowed to rotate and viscosity is measured at 0.2rpm.

Swelling index:²¹

The swelling index is the volume in ml taken up by the swelling of 1 gm of emulgel under specified condition. It is measured by taking one gram of emulgel formulation in aluminium foil place in beaker which contains 10ml of 0.1 N NaOH. The samples are taken at different time intervals and dry the sample. The weight of dried sample is measured.

Swelling index is calculated by using following formula:

Swelling Index (SW) % = [(Wt-W0)/W0] ×100

Drug Content Determination:²²

Weigh accurately 1gm of emulgel and dissolved in 100ml of phosphate buffer pH 7.4. The solution is sonicatedfor 2 hours to mix it properly. The solution is passed through the Whatmanfilter paper. Make appropriate dilution and the absorbance is measured spectrometrically at 375nm.

Drug content is determined using following formula:

Drug content= (concentration× dilution factor× volume taken) ×conversion factor.

Spreadability:^23,24

It is determined by apparatus suggested by Multimer et al (1956). It comprises of a wooden block. This block isequipped by pulley at one end. One glass slide is set on the wooden block. Excess amount of emulgel about 2 gm is deposit on this ground slide. Another glass slide is placed over applied emulgelwhich is furnished with the hook. On the top of the slides a 500gm weight is placed for 5 minutes to expel the air and to givethe uniform film of the emulgel between the slides. Excess of the emulgel is scrapped off from the edges. The top slide is then subjected to pull of 80 gm weight placed on pan attached to the pulley. The time (in seconds) required by the top slide to cover a distance of 7.5 cm be noted. A shorter interval indicates better Spreadability.

Spreadability measured by formula:

S = M × L / T

Where,

S = Spreadability

M = Weight tied to the upper glass slide

L = Length of the glass slide

T = Time in seconds

Extrudability study:^{25, 26}

The test is done to measure the force required to extrude the material from tube. The Pfizer hardness tester is used to determine the extrudability of emulgel. The aluminium tube filled with 15gm of emulgel attuned with the plunger. Pressure of 1kg/cm² is applied on this tube for 30sec. Then theextruded quantity of gel was weighed. Test is carried out in triplicate the average values are taken. More quantity of emulgel extruded having betterextrudability.

Extrudability iscalculated by usingfollowing formula:

Extrudability = Applied weight to extrude emulgel from tube (in gm)/Area (in cm2)

Globule size determination:

The emulgel sample were treated with scarlet red dye and spread on a glass slide as a thin film. This sample is observed under microscope. The measurements were carried at 25°C. The 1ml sample is diluted using double distilled water.

In vitro drug release study:^27,28

The in vitro drug release studies are carried out using Franz diffusion cell. The formulation about 1gm equivalent to 5mg is applied on egg membrane. The membrane is placed between donor and receptor compartment of cell. The receptor compartment is filled with 20ml of suitable buffer at maintained temp 37°C. This is stirred on magnetic stirrer. The 1ml sample is withdrawn at suitable time intervals and replaced with equal amt of fresh media. Samples analysed for drug content using UV visible spectrophotometer at particular wavelength.

Skin irritation study:²⁹

The test is carried out on ratskin. The hairs are removed from ratskin at 4 cm2 area. 0.5% of the emulgel sample is applied over this area. This skin surface is observed for redness, swelling after 24, 48 and 72hrs from application of formulation.

Stability studies:³⁰

The emulgel formulation is packed in aluminium collapsible tubes and stored at different temperature conditions for period of 3 months.

CONCLUSION:

After the extensive literature survey, we can conclude that emulgels has proven one of the most effective, convenient drug deliveries. The emulgel has ability to deliver hydrophobic as well as hydrophilic drug. Emulgels have high ability of penetration. Since emulgel possess good Spreadability, extrudability, viscosity, and becomes novel drug delivery to enhance the bioavailability of hydrophobic drugs.

REFERENCES:

1. AVS Madhu L, JN Suresh K, Sojana N, Mounika N, Priyanka G, Venkatesh A. Design and Optimization of Clotrimazole Emulgel by Using Various Polymers. Asian J. Pharm. Tech. 2021;11(1):41-47.

2. Sawant A. A, Mohite S.K. Formulation and Evaluation of Itraconazole Emulgel for Topical Drug Delivery. Asian Journal of Pharmacy and Technology. 2015;5(2):91-96.

3. Pravallika A, Priyanka R, Formulation and Evaluation of Aceclofenac Topical Emulgel. International Journal of Advanced Technology and Innovative Research. 2019;11(2):43-48.

4. Shaikh S. S, Parveen P, Shri Rekha M, Deepthi K, Sowjanya Ch, Seetha Devi A, Emulgel- A Novel Surrogate Approach for Transdermal Drug Delivery System. Indo American Journal of Pharmaceutical Research. 2014;4(11):1462-1472.

5. Redkar M. R, Hasabe P. S, Jadhav S. T, Mane P.S, Kare D. J. Review on Optimization Base Emulgel Formulation. Asian J. Pharm. Tech.2019;9(3):228-237.

6. Kalia Y. N, Guy R. H, Modeling Transdermal Drug Release. Adv Drug Deli Rev. 2001,48:159-72.

7. Ayub C.A, Gomes ADM, Lima MVC, Vianna-Soares CD, Ferreira LMA, Topical Delivery of Fluconazole: In Vitro Penetration and Permeation Using Emulsion as Dosage Forms, Drug. Dev. Ind. Pharm, 2007;33:273-280.

8. Kute S. B, Saudagar R.B, Emulsified Gel A Novel Approach for Delivery of Hydrophibic Drugs: An Overview. J. Adv. Pharm. Edu. & Research. 2013;3(4):368-379.

9. Phad A. R, Nandgude T. D, Ganapathy S. R, Emulgel: A Comprehensive Review for Topical Delivery of Hydrophobic Drugs. Asian Journal of Pharmaceutics. 2018;12(2):382-393.

10. Hasan S, Bhandari S, Sharma A, Garg P. Emulgel: A Review. Asian Journal of Pharmaceutical Research. 2021;11(4):263-8.

11. Pant S, Badola A, Pant W. A Review on Emulgel Novel Approach for Topical Drug Delivery System. World J. Pharm Sci. 2015;4:1728-43.

12. Ingle S, Tegeli V, Chandakavate B, Matole V, Kirdak O, Gophane G, Tonapr S, Birajdar A, Nangare S, Adlinge S, Ramansehetti S, Yadav k, Patil A, Khare A, Ubale S, Dulange V, Habib B, Mittha J. A Brief Review on Emulgel: A Novel Topical Drug Delivery System. Res. J. Pharma. Dosage Forms and Tech. 2021;13(1):25-30.

13. Krishna Veni N, Yashwanti P, Hemalata B, Padmalata K. A Review on Emulgels as a Novel Approach for Topical Drug Delivery. Asian Journal of Research in Pharmaceutical Science. 2022;12(2):163-8.

14. Samala M. L, Gowripattapu S, Role of Polymer as Gelling Agents in the Formulation of Emulgel. iMedPub Journals. 2016;2(1):1-8.

15. Das A, Ahemad A. B, Natural Permeation Enhancer for Topical Drug Delivery System and Permeation Evaluation: A Review. Asian Journal of Pharmaceutical and Clinical Research. 2017;10(9):5-9.

16. Khullar R, Kumar D, Seth Nimrata, Saini S, Formulation and Evaluation of Mefenamic Acid Emulgel for Topical Delivery. Saudi Pharmaceutical Journal. 2012; 20:63-67.

17. Eshwarnath S, Swetha K, Preethi P. J, Priyanka B, Reddy K. K. Emulgel: Review on Novel Approach to Topical Drug Delivery. Asian J. Pharm. Res.2014;4(1):4-11.

18. Ambhore N. P, Dandagi P. M, Gadad A. P, Mansora P, Formulation and Characterization of Tapentadol Loaded Emulgel for Topical Application. Indian Journal of Pharmaceutical Education and Research. 2017;51(4):525-535.

19. Vijaya Bhanu P, Shanmugam V, Lakshmi P. K, Development and Optimization of Novel Diclofenac Emulgel for Topical Drug Delivery. International Journal of Comprehensive Pharmacy. 2011;9(10):1-4.

20. Sheikh A. A, Siddiqui S. A, Siddiqui A. R, Zahid Z, Aejaz A, Formulation Development and Characterization of Aceclofenac Gel Containing Linseed Oil and Ginger Oleoresin. International Journal of Pharm Tech Research. 2011;3(3):1448-1453.

21. Yadav S, Mishra M, Tiwari A, Shukla A, Emulgel: A New Approach for Enhanced Topical Drug Delivery. International Journal of Current Pharmaceutical Research. 2017;9(1):15-19.

22. Mwangi A. N, Njogu P. M, Maru S. M, Njugna M, Njaria P. M, Kirirri G. K, Mathenge A.W, Meloxicam Emulgel for Topical Management of Rheumatism: Formulation Development, in vitro and in vivo Characterization. Saudi Pharmaceutical Journal. 2021; 29:351-360.

23. Bhosale M. S, Khade S, Patil A. S, Raut I. D, Manojkumar M, Jadhav K. K, Emulgel: A Novel Approach to Topical Drug Delivery. Levant Journal. 2021;20(7):394-406.

24. Amminbavi D, Lakshmi Prasanna N. Assessment of In Vitro Wound Healing Potential of Hibiscus Leaf Extract Emulgel. Asian J. Pharm.Res. 2020;10(2):67-72.

25. Gupta G.D, Gaud R.S. Release Rate of Nimesulide from Different Gellants. Indian J Pharm Sci. 1999; 61:229-234.

26. Shah R S. Formulation and Evaluation of Turmeric Emulgel. Asian Journal of Pharmacy and Technology. 2021;11(3):213-9.

27. Singh V, Singh S, formulation and Evaluation of Aceclofenac Topical Emulgels. InternationalJournal of Modern Pharmaceutical Research. 2021;5(4):151-157.

28. MakadiaH. A, Bhatt A. Y, Parmar R. B, Paun J. S, Tank H. M. Self-Nano Emulsifying Drug Delivery System (SNEDDS): Future Aspects. Asian Journal of Pharmaceutical Research. 2013;3(1):20-26.

29. Chaudhari P, Ajab A, Malpure P, Kolsure P, Sanap D, Development and in vitro evaluation of thermoreversible nasal gel Formulation of Rizatripan Benzoate. Indian J Pharm Educ Res. 2009; 43:55-62.

30. Shreevidya V.S, An overview on Emulgel, International Journal of Pharmaceutical and Phytopharmaceutical Research. 2019;9(1);92-97.

Received on 13.06.2022 Modified on 17.08.2022

Asian J. Res. Pharm. Sci. 2022; 12(4):335-340.

DOI: 10.52711/2231-5659.2022.00057

Sr. No	Drug	Marketed product	Manufacturer
1	Diclofenac sodium	Pennsaid	Nuva Pharma
2	Aceclofenac	Acent gel	Intas Labs India Pvt. Ltd
3	Diclofenac-diethyl-ammonium	Voltaren emulgel	Novartis Pharma
4	Clindamycin phosphate, Allantoin	Clingel	Stiefel Pharma
5	Clobetasol propionate	Topinate gel	Systopic Pharma
6	Metronidazole, Clindamycin	Lupigyl gel	Lupin pharma
7	Azithromycin	Avindo gel	Cosme Pharma Lab.
8	Diclofenac diethyl amine	Diclobar emulgel	Barakat Pharma
9	Benzoyl peroxide	Pernox gel	Cosme Remedies Ltd.
10	Clindamycin, Adapalene	Excex gel	Zee Laboratories