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International Journal of

Industrial Biotechnology and Biomaterials


ISSN: 2455-7323
Vol. 6: Issue 1
www.journalspub.com

Review on Development of Ethosomal Formulation of Ginger


S. Priyanka1, A. Krishna Shailaja2,*
1
Student, Department of pharmaceutics, Raja Bahadur Venkata Rama Reddy Women's
College, Osmania University, Hyderabad, Tamil Nadu, India
2
Teacher, Department of pharmaceutics, Raja Bahadur Venkata Rama Reddy Women's
College, Osmania University, Hyderabad, Tamil Nadu, India

ABSTRACT
Transdermal drug delivery, self-contained, discrete dosage forms which, when applied to the
skin, deliver the drug, through the skin at controlled rate to the systemic circulation.
Ethosomes, noninvasive delivery carriers that enable drugs to reach deep into the skin layers
or the systemic circulation which is made up of phospholipids, ethanol and water. This review
article summarizes structure, advantages, disadvantages, composition of ethosomes and
mechanism of drug penetration, method of preparation, evaluation and applications of
ethosomes, description about the plant, isolation of gingerol, preparation of ethosomal gel and
its evaluation.

Keywords: Ethosomes, transdermal, drug delivery, flavonoids, gingerol, transmission electron


microscope, Mayer’s Test, sonication

*Corresponding Author
E-mail: [email protected]

INTRODUCTION ginger root or ginger. It is a herbivorous


Transdermal drug delivery system (TDDS) perennial plant. Family: Zingiberaceae,
showed promising results compared to oral Genus Zingiber, Species: Z. officinale,
drug delivery system as it prevents Kingdom: Plantae.
gastrointestinal interferences and the drug's
first pass metabolism, but the main Pharmacological properties: Ginger is the
downside of TDDS is that it meets the herbal treatment for colds and other viral
barrier properties of Stratum Corneum, i.e. infections, poor appetite, digestive
only lipophilic drugs with molecular weight problems, arthritis and headache., Anti
<500 Da may move through it. To improve arthritic, Antioxidant, Anti-inflammatory
the permeation of drugs through the skin and Analgesic, Antiemetic, Anti-ulcer,
various mechanisms have been Antibacterial, Antiviral, Antifungal and
investigated, including use of chemical or Anti parasitic, Anti-ulcer, Anti-cancer
physical enhancer such as ethosomes have
been reported to enhance permeability of Chemical constituents: The major
drug through the stratum corneum barrier constituents in ginger rhizomes are
[1, 2]. Ginger (Zingiber officinale) is a carbohydrates (50–70%), lipids (3–8%),
flowering plant whose spice and folk terpenes, and phenolic compounds.
medicine are widely used as rhizome, Terpene components of ginger include

IJIBB (2020) 8–14 © JournalsPub 2020. All Rights Reserved Page 8


Review on Development of Ethosomal Formulation of Ginger Priyanka and Shailaja

zingiberene, β-bisabolene, α-farnesene, β- maceration process. solvent was evaporated


sesquiphellandrene, and curcumene, while by distillation to obtain thick pasty mass.
phenolic compounds include Gingerol, The thick pasty mass was suspended in
paradols, and shogaol. These Gingerol (23– water. The Ginger resin precipitates in
25%) and shogaol (18–25%) are found in water which was removed by filtration and
higher quantity than others. Besides these, the residue obtained was dried under
amino acids, raw fibre, ash, protein, vacuum. This extract was studied
phytosterols, vitamins (e.g., nicotinic acid phytochemically (Table 1).
and vitamin A), and minerals are also
present [3, 4]. ETHOSOMES
Ethosomes are mainly used for the delivery
Medicinal benefits: Ginger Contains of drugs through transdermal route. Drug
Gingerol, a medicinal substance with can be entrapped in ethosomes which have
powerful properties. Ginger Can Treat various physicochemical characteristics,
Several Types of Nausea, Morning i.e., Hydrophilic, lipophilic, or amphiphilic
Sickness in particular. Ginger Can Reduce Ethosomes are soft, malleable vesicles used
Soreness and Muscle Pain. The anti- for delivery of drug to reach the deep skin
inflammatory effects of osteoarthritis can layers and/or the systemic circulation The
be helpful. Ginger Can Drastically lower size range of ethosomes may vary from tens
blood sugars and increase risk factors for
of nano meters to microns. Ethosomes are
heart disease. Ginger Can Help Treat
modified forms of liposomes that are high
Chronic Indigestion. Ginger Powder may
reduce menstrual pain significantly. Ginger in ethanol content [5].
May Lower Cholesterol Levels. Ginger
Produces Material That Can Aid Cancer
Prevention. Ginger May Improve Brain
Function and Protect Against Alzheimer's
Disease [5].

Isolation and Standardization of Gingerol:


Dry ginger was crushed to a coarse powder
and extracted with95% ethanol by simple Fig. 1. Composition of Ethosome.

Table 1. Phytochemical screening of ginger extract.


Phytochemicals Tests Reagent Positive result
Alkaloids Dragendorff test Dragendorff reagent Wagner’s Prominent yellow ppt. Reddish
Wagner’s test Mayer’s reagent 1% HCl, Mayer’s reagent brown ppt. Turbid extract is
test obtained
Flavonoids Ammonia test sodium 1% NH3 20% NaOH, HCl Yellow colour Yellow colour turns
hydroxide test to colourless
Tannins Ferric chloride test 5% FeCl3 Blue-Black or blue green
colouration
Phenolic Gelatin test Lead acetate 1% gelatin solution containing 10% White ppt. Bulky white ppt.
compounds test NaCl, 10% lead acetate
Saponins Foam test 20% distilled water (mixed Presence of froth
vigorously for 15 minutes )
Terpenoids Salkowski test 0.5 ml chloroform,1ml conc. H2SO4 Reddish brown colouration at the
interface
Carbohydrates Molisch test Fehling’s Conc. HCl and Mg turnings Violet ring Yellow and brick red
test ppt
Proteins Biuret test 4% NaOH, 1% CuSO4 Violet or pink colour
Glycosides Legal’s test Keller killani Pyridine, Sodium nitroprusside Pink or red colour Reddish brown
test Glacial acetic acid, 5% FeCl3 and bluish green colour

IJIBB (2020) 8–14 © JournalsPub 2020. All Rights Reserved Page 9


International Journal of Industrial Biotechnology and Biomaterials
ISSN: 2455-7323
Vol. 6: Issue 1
www.journalspub.com

Table 2. Formulation components of ethosomes.


Class Examples Uses
Phospholipid Soya phosphatidylcholine, Egg phosphatidylcholine, Vesicles forming component.
Dipalmitoylphosphatidylcholine, Distearoyl
phosphatidylcholine
Polyglycol Propylene glycol, Transcutol As a skin penetration enhancer
Alcohol Ethanol, Isopropyl alcohol For providing the softness for vesicle
membrane, As a penetration enhancer
Cholesterol Cholesterol For providing the stability to vesicle
membrane
Dye Rhodamine-123, Rhodamine Red, Fluorescein isothiocyanate For characterization study.
(FITC), 6-carboxy fluorescence
Vehicle Carbopol D934 As a gel former.

The ethosomal system is composed of Ethosomal drug delivery is very simple in


phospholipid, high concentration of alcohol comparison to iontophoresis and
and water. The high concentration of phonophoresis and other complicated
ethanol makes ethosomes unique because methods [7].
ethanol causes disturbance of skin lipid
bilayer organization, hence when METHODS OF PREPARATION
incorporated into a vesicle membrane, it Cold Method
enhances the vesicles ability to penetrate in It is the most popular approach used for
to stratum corneum. Ethosomal Altering ethosomal formulating preparation.
alcohol can modulate the drug delivery:
water or alcohol: polyol: water ratio. Phospholipid, medication, and other lipid
Ethosomes are vesicular carrier consisting materials are blended in this process.
of hydro alcoholic or hydro/alcoholic/ During stirring, propylene glycol or another
glycolic phospholipid in which alcohol polyol is added. This mixture is in a water
concentrations or combinations of alcohols bath heated to 30°C. In a separate vessel,
are relatively high (Figure 1). The various the water heated to 30°C is added to the
type of additives used in ethosomes are mixture which is then stirred in a covered
shown in Table 2 [6]. vessel for 5 min. Using the method of
sonication or extrusion, the vesicle sizes
Advantages of Ethosomal Drug delivery: can be reduced to seek extension. Finally,
Ethosomal drug delivery system has much the formulation is stored in fridge [8, 9]
advantage as compared to other (Figure 2).
transdermal and dermal delivery systems.
These advantages include (1) Enhanced Hot Method
permeation of drug through skin for In this process, phospholipid is distributed
transdermal drug delivery. (2) Ethosomes in water until a colloidal solution is
provide platform for the delivery of large obtained by heating in a water bath at
and diverse group of drugs across the 400°C. Ethanol and propylene glycol are
skin. (3) Ethosomes contain non-toxic combined in a separate vessel and heated to
materials in formulation, ethosomal drug 400°C. The organic phase is added to the
is administered in semisolid form hence aqueous one once both mixtures reach
producing high patient compliance. (4) 400°C. The drug is dissolved in water or
Ethosomal drug delivery system can be ethanol depending on its hydrophilic/
used widely in pharmaceutical, veterinary hydrophobic properties. The vesicle size of
cosmetic fields. (5) Ethosomal system is ethosomal formulation can be decreased to
passive, non-invasive and is available for the desired extent using probe sonication or
immediate commercialization. (6) extrusion methods [10, 11] (Figure 3).

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Review on Development of Ethosomal Formulation of Ginger Priyanka and Shailaja

Fig. 2. Cold method Flow diagram.

Fig. 3. Hot method flow diagram.

MECHANISM OF ACTION OF Ethosomes effect: Increased lipid fluidity in


ETHOSOMES the cell membrane caused by ethosomal
The mechanism of the drug absorption from ethanol results in increased permeability of
ethosomes is not clear. The drug absorption the skin. The ethosomes permeate the deep
probably occurs in following two phases skin layers very easily, where they are fused
[12] (Figure 4). with skin lipids and release the drugs into
the deep skin layer [14].
Ethanol effect: Ethanol acts through the
skin as a piercing enhancer. The Characterization of Ethosomes
penetration enhancing impact mechanism 1. Detection of particle size and zeta
is well known. Ethanol penetrates into potential: Using a computerized
intercellular lipids and increases the inspection system and photon
fluidity of cell membrane lipids and correlation spectroscopy (PCS),
decrease the density of lipid multilayer of Dynamic light scattering (DLS).
cell membrane [13]. 2. Clogging medications: The efficacy of

IJIBB (2020) 8–14 © JournalsPub 2020. All Rights Reserved Page 11


International Journal of Industrial Biotechnology and Biomaterials
ISSN: 2455-7323
Vol. 6: Issue 1
www.journalspub.com

ethosomes in the trapping can be acyclovir ethosomal preparation compared


calculated using the technique of to the 5% acyclovir cream showed
ultracentrifugation. significant improvements in treatment of
3. The transition temperature of the lipid herpetic infections.
vesicular structures can be calculated
using differential calorimetry scanning. Trans cellular Deliver-Ethosomes-as
4. Content on drugs: Using UV compared to the marketed formulation
spectrophotometer, the ethosomal drug suggested ethosomes to be an attractive
content may be determined. This may clinical alternative for anti-HIV therapy
also be quantified using a modified [17, 18].
chromatographic high-performance
liquid method. Ethosomes are used in pilosebaceous
5. Measuring surface tension: The surface targeting-Ethosomes, high ethanol
tension activity of the drug in aqueous containing vesicles are capable of
solution can be measured in a Du Nouy penetrating deeper layers of the skin and
ring tensiometer using ring method thus appear to be vesicles of choice for the
6. Stability studies: vesicle stability can be transdermal drug delivery of hydrophilic
determined over time by evaluating and impermeable drugs through the skin.
vesicle size and structure. Mean size is Transdermal Hormone delivery-Oral
measured by dynamic light scattering, hormone administration is associated with
and changes in structure are observed problems such as high first-pass
by Transmission Electron Microscope. metabolism, poor oral bioavailability and
7. Skin permeation studies: Use of numerous dose-dependent side effects, the
confocal laser scanning microscopy risk of medication failure with each missed
(CLSM) to assess the ability of pill is known to increase. Delivery of Anti-
ethosomal preparation to penetrate the Arthritis Drug-Topical delivery of anti-
skin layers [15, 16]. arthritis drug is a better option for its site-
specific delivery and overcomes the
Therapeutic Applications of Ethosomes problem associated with conventional oral
In the treatment, herpetic infection, 5% therapy [19, 20].

Fig. 4. Mechanism of action.

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Review on Development of Ethosomal Formulation of Ginger Priyanka and Shailaja

LIMITATIONS OF ETHOSOMES For Transdermal Drug Delivery


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ineffective then ethosomes may Pharmaceutical And Clinical
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organic to water media [21]. highly efficient formulation of
diclofenac for the topical, transdermal
CONCLUSIONS administration in ultra deformable
Transdermal route offers several drug carriers, Transfersomes.
advantages over conventional route in Biochimica et Biophysica Acta. 2001,
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that Ethosomes provide better skin Opanasopit, Theerasak Rojanarata,
penetration and noninvasive drug delivery and Tanasait Ngawhirunpat.
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layers of the skin. I concluded that firstly Permeation of Meloxicam-Loaded
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Yong Zhao, Shujin Ma, Wenjing Li,
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International Journal of Industrial Biotechnology and Biomaterials
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Vol. 6: Issue 1
www.journalspub.com

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Cite this Article: S. Priyanka, A. Krishna Shailaja. Review on


Development of Ethosomal Formulation of Ginger. International Journal
of Industrial Biotechnology and Biomaterials. 2020; 6(1): 8–14p.

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