Emulgel A Reliable System for Topical Delivery of Lipophilic Drugs in Present Scenario: Review

 

Rishu Yadav1,3, Narendra Kumar Pandey1, Rajiv Kukkar2, Deepika Dutta3, Preeti Avasthi3

Monika Rana3, Swati Modgil3

1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

2Raffles University, Neemrana, Rajasthan, India.

3Maharaja Agrasen University, Baddi, H.P. India.

*Corresponding Author E-mail: rishu.yadav789@gmail.com

 

ABSTRACT:

Topical drug delivery can be defining as good delivery system for drugs, in which drug directly get interact with skin and give its pharmacological effect to desired site to cure and treat variety of disorder. Gel has major disadvantage because it cannot prepare for hydrophobic drugs this type of limitation can be defeated by emulgel. Emulgel have dual property like emulsion and gel and gives dual release system. Primary disadvantage of lipophilic drug that it does not dissolves in aqueous solvent and cause problem in drug delivery. Emulgels gives a good advantage over gel that hydrophobic drugs are easily dissolve in oil phase and then added in aqueous phase to form w/o type emulsion. These emulgel then incorporate into gel to form emulgel. Emulgel are good carrier for topical delivery of lipophilic drugs and have several advantages over different drug delivery system. Emulgel give better patient compliance and promote controlled pattern of drug delivery due to presence of cross linked structure of gelling agent. Emulgels formulations can be used for anti-inflammatory, analgesic, antifungal, acne, skin disorder and also in form of cosmetic products.

 

KEYWORDS: Topical, Emulgel, Lipophilic Drugs, Hydrophobic Drugs W/O Emulsion.

 

 


INTRODUCTION:

Most accepted route for drug delivery is oral route, beside this parental, sublingual, subcutaneous and vaginal routes are also used, In few cases drug does not give pharmacological response by oral  route due to their low absorption, structure, lipophilicity, poor bioavailability and also produce serious side effects by oral route1,2. This needs to prepare topical drug delivery system which can easily deliver the drug3,4,5. Among this gel is prepared to defeat such kind of problem, now a days nanogel is better option6. Gel has one major disadvantage that it could not be prepare for lipophilic drug7,8,9. Emulgel are the best carrier to deliver such kind of drugs topically because it easily bounds lipophilic drugs10.

 

Due to oil phase present in system and has dual release pattern like gel as well as emulsion to give controlled release system for drugs which have small plasma half life11,12. Emulgel also enhance the solubility of lipid soluble drugs13. When gel and emulsion are added together then emulgel is found, for hydrophilic drugs water in oil type of emulsion is synthesized14. Lipophilic drugs oil in water type of emulsion is prepared15. Emulgel has several property like thixotropic, higher penetration to skin, higher spreadability, ease to apply, easy to remove, non-greasy, better patient compliance, bio friendly, water soluble and have larger shelf life16. Drug can enter into skin via three different routes first one is stratnum corneum, second oil gland and third sweat ducts17. Stratnum corneum consist of 99% overall skin surface and also convenient for percutaneous absorption18. There are several factors which consider for percutaneous absorption are partition coefficient (drug delivery from vehicle), diffusion coefficient (diffusion of drug through skin), and concentration gradient19.

 

Advantages:

·       Enhance solubility

·       Bypass first pass liver metabolism

·       Better patient compliance

·       Site specific delivery

·       Controlled release system

·       Ease of application

·       Drug which have shorter half-life can be use in this system

·       Avoidance of toxicity cause by drug taken orally

 

Disadvantages:

·       Dermatitis and skin irritation

·       Some allergic reaction

·       Drug which have Lager particle size cannot absorb easily through skin

 

Components of emulgel:

·       Oil phase in this phase oil is used. It contains mineral oils, aromatic oils, liquid paraffin etc

·       Aqueous phase this phase is consist of either water or alcohol. Drug components mainly add in this phase.

·       Emulsifying agent these agents promote emulsification, and also gives a stable formulation. PEG 40, Tween 80 and Span 80 are mainly used as emulsifying agent.

·       Gelling agent this agent gives a good consistency and thickens to the formulation, called gelling agent carbopol 940­-934, and HPMC mainly used as gelling agent.

·       Permeation enhancers these are used to increase the permeability of stratnum corneum. These acts by reversible changing in the skin constituents produce a temporary effect. Oleic acid, lecithin, urea clove oil, menthol, linoleic acid and isopropyl meristate basically used in the form of permeation enhancers.

 

Characteristics of Permeation enhancers:

·       It should not be reactive

·       It should not react with other body components

·       It should work in a unidirectional way

·       It should not get react with receptors which are existing in the body

 

Mechanism of Permeation enhancers:

Permeations enhancers are act by creating the disruption of stratnum corneum lipids and get interact with protein present in intercellular space and enhance the entry of the drug to the lipid surface.

 

Method of Preparation:

·       Preparation of gel phase, first of all weighed carbopol 940 and mix it with distilled water with constant stirring. Then adjust the Ph from range 6-6.5 with triethenolamine.

·       Preparation of oil phase, this phase contains oil i.e liquid paraffin and span 80.

·       Preparation of aqueous phase these phases contains either distilled water or alcohol and add tween 80.

 

Add propyl and methyl paraben in polyethylene glycol and mixed it in aqueous phase whereas dissolve the drug in ethanol and also mix in aqueous phase. Then heat the oil and aqueous phase separately at 70-80C and allow it to cool at room temperature and then add aqueous phase in oil phase. Add glutaraldihyde during mixing of emulsion and gel in ratio of 1:1 to obtain emulgel

 

Evaluation of Emulsion:

1.     Globule size measurement:

Globule size of emulgel was measured by Scanning electron microscopy. Taken 1ml of emulgel and diluted up to 10ml with distilled water and then takes 1ml of diluted emulgel with micropipette in aluminium foil. Place this aluminium foil in Petri dish and allow it to dry at room temperature for 24hours. Then placed the sample in sample holder and captured pictures from different angle.

 

2.     Zeta potential:

Zeta potential indicated the stability of formulation and measured by Zetasizer. Accurately weighted 1ml emulgel then diluted up to 10ml and Place the sample in cuvette at 25⁰C. Reading was estimated by zetasizer.

 

Evaluation of Emulgel:

1.     Physical appearance:

The emulgel is tested for physical evaluation like colour, texture, homogeneity and pH Digital pH meter was used to determine the Phof emulgel.

 

2.     Drug content:

Drug content is revealed by mixing emulgel in an appropriate solvent and filters it to remove impurities. Then filtrate is utilized to take absorbance in UV spectrophotometer. Put the absorbance in standard equation to calculate the drug content.

 

3.     Spread ability:

Spread ability was calculated by using the diameter of emulgel which was placed between the two glass slides by applying appropriate pressure. 350mg of emulgel was taken in one glass slide and the other glass side drop over it from the distance of 5cm, the diameter covered by emulgel was calculated.

 

4.     Viscosity:

Viscosity of emulgel was measured at 25⁰C with brook field viscometer at different rpm.

 

5.     Swelling index:

Accurately weighted 1gm emulgel and placed it onporous aluminium foil containing 0.1 N NaOH in beaker withdrawn sample at different time interval and weight was measured.

 

Swelling index = Wt- Wo / Wo Χ 100

Wt = weight after time t

Wo = initial weight

 

6.     Skin irritation test:

Skin irritation study was carried out in Wistar rats. Firstly shaved the ratskin and applied emulgel on shaved skin and evaluated up to 24hours for any changes in skin like change in colour, swelling, redness etc.

 

7.     In Vitro study:

In this study Franz diffusion shell was used. Egg membrane was removed from egg by using HCl and tied up between donor and receptor compartment of Franz diffusion cell. The donor compartment contains formulation and receptor contains the PBS (phosphate buffer) of pH 5.5 sample was stirred with magnetic stirrer and collected at different time interval. Absorbance was taken by UV spectrophotometer and placed in standard equation to get the drug content.

 

8.     Ex Vivo study:

Rat skin was used to perform this study. Skin is hydrated before placing in Franz diffusion cell. Donor compartment contains the rat skin and receptor contains PBS (phosphate buffer) of pH 5.5. Apply the emulgel formulation on the upper surface of rat skin and allowed it to stir by using magnetic stirrer. Temperature of system should be controlled within the range of 37+5⁰C. At different time interval sample was withdrawn and absorbance was taken by UV spectrophotometer, then calculate the drug content by using standard equation.

 

9.     Retention of drug in dermal layer:

After completion 12hours of Ex Vivo study emulgel residue which was present in dermis layer was determined. This dermis was cut into several tiny segments and homogenized it in homogenizer at 3000 rpm for 15 min and the homogenate was filtered, filtrate was again  apply to centrifuge for 10 min at 10000rpm . Supernatant was used for calculation and estimate the absorbance with UV spectrophotometer. Place this absorbance reading in standard equation to calculate the amount of drug which is remained on dermis layer.

 

10. Stability studies:

According to the ICH guidelines of stability the formulation was kept in stability chamber for 3 months at different temperature and humidity. 30⁰C +- 2 at 65% Rh for long term stability and sample was withdrawn every month for accelerated stability temperature is scheduled 40⁰C ± 2 at 75% Rh and sample was withdrawn after 3 months to evaluate the drug content and release.

 

11.  Drug Kinetic release profile:

To explore the drug kinetic release profile from formulation different mathematical methods applied. Like zero order, first order, Higuchi′s model and Korsmeyer and Peppas model.

 

APPLICATIONS:

·       Lipophilic drugs can effortlessly combines into gel

·       Controlled release pattern of drug which have smaller half life

·       Gives better patient compliance

·       Being  gelling nature it gives a good spreadability and easy to apply

·       Economical friendly i.e. it can formulate in very reasonable price

·       It gives the better stability than other dosage form

·       It has the good loading capacity then niosome, liposome SLN and NLC

·       It enhances solubility of lipophilic drugs

 

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Received on 25.03.2021           Modified on 25.06.2021

Accepted on 20.08.2021         © RJPT All right reserved

Research J. Pharm. and Tech. 2022; 15(6):2845-2848.

DOI: 10.52711/0974-360X.2022.00475