2. ETHOSOMES : A NOVEL DRUG DELIVERY SYSTEM
Seminar on Recent Trends
Presented By :
Nirali N. Dave
B.Pharm
Guided By:
Mr. Sameer Sheikh
Department of Pharmaceutics 2
P. Wadhwani College Of Pharmacy, Yavatmal
3. CONTENTS
Introduction to TDDS
Skin
Ethosomes
Advantages
Disadvantages
Mechanism of penetration
Additives used in ethosomes
Preparation of ethosomes
Characterization of ethosomes
Applications
Future aspects
Conclusion 3
References
4. INTRODUCTION TO TDDS
Definition: Transdermal drug delivery systems
are defined as self-contained, discrete dosage
forms which, when applied to the intact
skin, deliver the drug, through the skin, at
a controlled rate to the systemic circulation
For transdermal delivery of drugs, stratum
corneum (SC) is the main barrier for
permeation of drug.
Now a days
liposomes, niosomes, transferosomes and
ethosomes (vesicular and non invasive drug
delivery)are used to increase the permeation
of drug through the stratum corneum. 4
7. Possible
pathways for a
penetrant to cross
the skinbarrier. (1)
across the intact
horny layer, (2)
throughthe hair
follicles with the
associated
sebaceous
glands, or (3) via
the sweat glands
7
8. THE NON-INVASIVE APPROACHES FOR PROVIDING TRANSDERMAL DRUG
DELIVERY OF VARIOUS THERAPEUTICS SUBSTANCES ARE1
1) Drug and vehicle interactions
a) Selection of correct drug or prodrug
b) Chemical potential adjustment
c) Ion pairs and complex coacervates
d) Eutectic systems
2) Stratum corneum modification
a) Hydration
b) Chemical penetration enhancers
3) Stratum corneum bypassed or removed
a) Microneedle array
b) Stratum corneum ablated
c) Follicular delivery 8
9. APPROCHES …
4) Electrically assisted methods
a) Ultrasound ( Phonophoresis, Sonophoresis )
b) Iontophoresis
c) Electroporation
d) Magnetophoresis
e) Photomechanical wave
5) Vesicles and particles
a) Liposomes and other vesicles
b) Niosomes
c) Transfersomes
9
10. ETHOSOMES
Ethosomes are noninvasive delivery carriers that enable drugs
to reach the deep skin layers and/or the systemic circulation.
Ethosomes are “soft vesicles” represents novel vesicular carries
for enhanced delivery of active agents to/through skin.
They are composed mainly of phospholipids,
(phosphatidylcholine, phosphatidylserine, phosphatitidic acid),
high concentration of ethanol and water [3].
The size of Ethosomes vesicles can be modulated from tens of
nanometers to microns.
Touitou discovered and investigated lipid vesicular systems
embodying ethanol in relatively high concentration and named
10
them ethosomes [8].
11. INFLUENCE OF HIGH ALCOHOL CONTENT
Ethanol is an established efficient permeation
enhancer[4,5].
The concentration of ethanol (20-50%) in vesicular
form in ethosomes is the main reason for their
better skin permeation ability.
Due to high ethanol concentration the ethosomal
lipid membrane was packed less tightly than
conventional vesicles but possessed equivalent
stability as other vesicular delivary systems.
11
12. ADVANTAGES
Enhanced permeation of drug through skin.
Ethosomes are platform for the delivery of large and diverse
group of drugs.
Ethosome composition is safe and the components are approved
for pharmaceutical, veterinary and cosmetic use.
Low risk profile.
Better patient compliance: can be used in the form of gel, patch.
It contains non‐toxic raw material in formulation.
Relatively smaller size as compared to conventional vesicles
Better stability and solubility of many drugs as compared to
conventional vesicles 12
13. DISADVANTAGES
Poor yield.
If shell locking is ineffective then the coalescence of
ethosomes may occur and fall apart on transfer into
water.
Loss of product during transfer from organic to water
media.
13
14. MECHANISM OF DRUG PENETRATION
1. Ethanol effect
Ethanol acts as a penetration enhancer through the skin.
Ethanol penetrates into intercellular lipids and increases the fluidityof
cell membrane lipids and decrease the density of lipid multilayerof
cell membrane.
2. Ethosomes effect
Increased cell membrane lipid fluidity caused by the ethanol results
increased skin permeability.
The ethosomes permeates very easily inside the deep skin layers,
where it got fused with skin lipids and releases the drugs into deep
layer of skin. 14
16. DIFFERENT ADDITIVES EMPLOYED IN
FORMULATION OF ETHOSOMES
Class Example Uses
Phospholipid Soya phosphatidyl choline Vesicles forming component
Egg phosphatidyl choline
Dipalmityl phosphatidyl choline
Distearyl phosphatidyl choline
Polyglycol Propylene glycol As a skin penetration enhancer
Transcutol RTM
Alcohol Ethanol For providing the softness for vesicle
Isopropyl alcohol membrane
As a penetration enhancer
Cholesterol Cholesterol For providing the stability to vesicle
membrane
Dye Rhodamine-123 For characterization study
Rhodamine red
Fluorescene Isothiocynate (FITC)
6- Carboxy fluorescence
16
Vehicle Carbopol Ð934 As a gel former
17. METHOD FOR PREPARING ETHOSOMES
There are two methods for preparing ethosomes:
1. Cold Method
2. Hot method
17
20. CHARACTERIZATION OF ETHOSOMES
Visualization
Vesicle Size and Zeta potential
Entrapement Efficiency
Transition Temperature
Surface Tension Activity Measurement
Vesicle Stability
Penetration and Permeation studies
20
21. CHARACTERIZATION OF ETHOSOMES , CONT…
1. Visualization : Visualization by electron
microscopy reveals an ethosomal formulation
exhibited vesicular structure 300-400 nm in
diameter.
21
22. CHARACTERIZATION OF ETHOSOMES , CONT…
2. Vesicle Size and Zeta potential :
Particle size and zeta potential can be determined bt
DLS and PCS.
As the alcohol concentration increases the vesicular
size decreases.
As the phospholipid concentration increases the
vesicular size increase
22
24. CHARACTERIZATION OF ETHOSOMES , CONT…
3. Entrapement Efficiency :
This is measured by the Ultra centrifugation
technique.
4. Transition Temperature :
This is determined by using Differential Scanning
Calorimetry (DSC)
5. Surface Tension Activity Measurement :
The surface tension activity of drug in aq. solution
can be measured by the ring method in a Du Nouy
ring tensiometer.
24
25. CHARACTERIZATION OF ETHOSOMES , CONT…
6. Vesicle Stability :
This is measured by DLS
and structure changes
are observed by TEM.
7. Penetration and
Permeation studies :
Depth of penetration from
ethosomes can be
visualized by confocal
laser scanning.
Srudy of permeation characteristics 25
of
the drug zidovudine by various routes
26. DIFFERENT STUDIES RELATED TO THE APPLICATION OF
ETHOSOMES AS A CARRIER SYSTEM
Pilosebaceous Targeting
Transdermal Delivery of Hormones
Delivery of anti-parkinsonism agent
Transcellular Delivery
Topical Delivery of DNA
Delivery of Anti-Arthritis Drug
Delivery of Antibiotics
Delivery of Anti-Viral Drugs
Delivery of Problematic drug molecules
26
27. PILOSEBACEOUS TARGETING
Hair follicles and sebaceous glands are increasingly
being recognized as potentially significant elements in the
percutaneous drug delivery.
Interest in pilosebaceous units has been directed
towards their use as depots for localized therapy,
particularly for the treatment of follicle-related disorders
such as acne or alopecia. Furthermore, considerable
attention has also been focused on exploiting the follicles
as transport shunts for systemic drug delivery .
Minoxidil is a lipid-soluble drug used topically on the scalp
for the treatment of baldness by pilosebacious delivery.
27
28. TRANSDERMAL DELIVERY OF HORMONES
Oral administration of hormones is associated with
problems like high first pass metabolism, low oral
bioavailability and several dose dependent side Effects.
Transdermal delivery of hormones increased the
absorption of drug
Eg: Nearly 30-times higher skin permeation of
testosterone from ethosomal formulation as compared
to that marketed formulation. The amount of drug
deposited was significantly higher in case of ethosomal
formulation
28
29. DELIVERY OF ANTI-PARKINSONISM AGENT
Ethosomal formulation of psychoactive drug
trihexyphenidyl hydrochloride (THP) and compared
its delivery with that from classical liposomal
formulation. THP is a M1 muscarinic receptors
antagonist and used in the treatment of Parkinson
disease.
THP has a short biological half-life (3hr) and its oral
administration is difficult due to motor disorders and
neurogical manifestations associated with
parkinsonian syndrome .
skin permeation potential of ethosomal-THP
formulation and its use for better management of
Parkinson disease. 29
30. DELIVERY OF ANTIBIOTICS
Topical delivery of antibiotics is a better choice for increasing the
therapeutic efficacy of these agents.
Conventional oral therapy causes several allergic reactions
along with several side effects. Conventional external
preparations possess low permeability to deep skin layers and
subdermal tissues .
Ethosomes can circumvent this problem by delivering sufficient
quantity of antibiotic into deeper layers of skin.
Ethosomes penetrate rapidly through the epidermis and bring
appreciable amount of drugs into the deeper layer of skin and
suppress infection at their root.
The results of this study showed that the ethosomal formulation
of antibiotic could be highly efficient and would over come the 30
problems associated with conventional therapy.
31. DELIVERY OF ANTI-VIRAL DRUGS
Zidovudine is a potent antiviral agent acting on acquired
immunodeficiency virus. Oral administration of zidovudine is
associated with strong side effects.
Ethosomes could increase the transdermal flux, prolong the
release and present an attractive route for sustained delivery of
zidovudine.
Acyclovir is another anti-viral drug that widely used topically for
treatment of Herpes labialis .
The conventional marketed acyclovir external formulation is
associated with poor skin penetration of hydrophilic acyclovir to
dermal layer resulting in weak therapeutic efficiency .
It is reported that the replication of virus takes place at the basal
dermis .
Significant improvement in all evaluated clinical parameters was
observed when disorder was treated with ethosomal formulation
in comparison to marketed formulation. 31
32. Drug Applications Comments
Acyclovir Treatment of Herpetic Improved drug delivery
infection
Zidovudine Treatment of AIDS Improved transdermal flux
Trihexypenidyl HCl Treatment of Parkinsonian Increased drug entrapment
syndrome efficiency, reduced side effect &
constant systemic levels
Erythromycin Efficient healing of S. aureus Improved drug penetration and
- systemic effect.
induced deep dermal
infections
Insulin Treatment of Diabetes Improved therapeutic efficacy
ofdrug
Testosterone Treatment of male Enhance skin permeation
hypogonodism
Cannabidol Prevents inflammation and Significant accumulation of the
edema drug in the skin
Minodixil Hair growth promotion effect Higher skin retention
32
Bacitracin Treatment of dermal Reduced drug toxicity
infections
33. FUTURE ASPECTS
Introduction of ethosomes has initiated a new area in
vesicular research for transdermal drug delivery.
Different reports show a promising future of ethosomes in
making transdermal delivery of various agents more
effective.
Further, research in this area will allow better control over
drug release in vivo, allowing physician to make the therapy
more effective.
Ethosomes offers a good opportunity for the non-invasive
delivery of small, medium and large sized drug molecules.
The results of the first clinical study of acyclovir-ethosomal
formulation support this conclusion.
Thus, it can be a logical conclusion that ethosomal
formulations possess promising future in effective 33
dermal/transdermal delivery of bioactive agent.
34. CONCLUSION
Ethosomes are characterized by simplicity in their
preparation, safety and efficacy and can be
tailored for enhanced skin permeation of active
drugs.
Ethosomes have been found to be much more
efficient at delivering drug to the skin.
Ethosomes have been tested to encapsulate
hydrophilic drugs, cationic drugs, proteins and
peptides.
Most of the device-induced transdermal drug
delivery techniques are still in the early stages of
commercialization. 34
35. REFERENCES
[1] Albery, W.J. and Hadgraft, J. (1979) J. Pharm. Pharmacol. 31,129-139.
[2] Kanitakis, J. (2002) Eur. J. Dermatol. 12, 390-399.
[3] Barry, B.W. (2001) Eur. J. Pharm. Sci. 14, 101-114.
[4] Hadgraft, J. (2001) Skin Pharmacol. Appl. Skin. Physiol. 14, 72-81.
[5] Braun-Falco, O.; Kortung, H.C.; Maibach, H.I. Liposome Dermatitis, Springer-Verlag, Berlin
Heideberg, 1992.
[6] Touitou, E. Composition of applying active substance to or through the skin., US patent,
5,716,638, 1996.
[7] Touitou, E. Composition of applying active substance to or through the skin., US patent,
5,540,934, 1998
[8] Jain, S.; Umamaheshwari, R.B.; Bhadra, D.; Jain, N.K. (2004) Ind. J. Pharm. Sci. 66(1), 72-
81.
[9] Verma, D.D. and Fahr, A. (2004) Synergistic penetration effect of ethanol and phospholipids
on the topical delivery of Cyclosporin A. J. Control Release. 97, 55-66.
[10]vanden Berge, B.A.I.; Swartzendruber, V.A.B.; Geest, J. (1997) J. Microsc., 187, 125-133.
[11] Ogiso, T.; Yamaguchi, T.; Iwaki, M.; Tanino T.; Miyake. Y. (2001) J. Drug Targeting. 9(1), 49-
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[12] Grams, Y.Y. and Bouwstra, J.A. (2002) J. Control Release. 83, 253-262. 35
