Ethosomes : Novel Drug Delivery


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Ethosomes : Novel Drug Delivery

  1. 1. Welcome 1
  2. 2. ETHOSOMES : A NOVEL DRUG DELIVERY SYSTEM Seminar on Recent TrendsPresented By :Nirali N. DaveB.PharmGuided By:Mr. Sameer Sheikh Department of Pharmaceutics 2 P. Wadhwani College Of Pharmacy, Yavatmal
  3. 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. 4. INTRODUCTION TO TDDSDefinition: 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
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  6. 6. LAYERS OF SKIN3 layers:Epidermis: Stratum corneum Stratum granulosum Stratum spinosum Basal layerDermis: Papillary dermis layer Reticular dermis layerSub cutaneous layer 6
  7. 7. Possiblepathways for apenetrant to crossthe skinbarrier. (1)across the intacthorny layer, (2)throughthe hairfollicles with theassociatedsebaceousglands, or (3) viathe sweat glands 7
  8. 8. THE NON-INVASIVE APPROACHES FOR PROVIDING TRANSDERMAL DRUG DELIVERY OF VARIOUS THERAPEUTICS SUBSTANCES ARE11) 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. 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. 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. 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. 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. 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. 14. MECHANISM OF DRUG PENETRATION1. 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. 16. DIFFERENT ADDITIVES EMPLOYED IN FORMULATION OF ETHOSOMES Class Example UsesPhospholipid Soya phosphatidyl choline Vesicles forming component Egg phosphatidyl choline Dipalmityl phosphatidyl choline Distearyl phosphatidyl cholinePolyglycol Propylene glycol As a skin penetration enhancer Transcutol RTMAlcohol Ethanol For providing the softness for vesicle Isopropyl alcohol membrane As a penetration enhancerCholesterol Cholesterol For providing the stability to vesicle membraneDye Rhodamine-123 For characterization study Rhodamine red Fluorescene Isothiocynate (FITC) 6- Carboxy fluorescence 16Vehicle Carbopol Ð934 As a gel former
  17. 17. METHOD FOR PREPARING ETHOSOMESThere are two methods for preparing ethosomes:1. Cold Method2. Hot method 17
  18. 18. COLD METHOD 18
  19. 19. HOT METHOD 19
  20. 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. 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. 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
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  24. 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. 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. 26. DIFFERENT STUDIES RELATED TO THE APPLICATION OFETHOSOMES 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. 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. 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. 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. 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. 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. 32. Drug Applications CommentsAcyclovir Treatment of Herpetic Improved drug delivery infectionZidovudine Treatment of AIDS Improved transdermal fluxTrihexypenidyl HCl Treatment of Parkinsonian Increased drug entrapment syndrome efficiency, reduced side effect & constant systemic levelsErythromycin Efficient healing of S. aureus Improved drug penetration and - systemic effect. induced deep dermal infectionsInsulin Treatment of Diabetes Improved therapeutic efficacy ofdrugTestosterone Treatment of male Enhance skin permeation hypogonodismCannabidol Prevents inflammation and Significant accumulation of the edema drug in the skinMinodixil Hair growth promotion effect Higher skin retention 32Bacitracin Treatment of dermal Reduced drug toxicity infections
  33. 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. 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. 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- 53[12] Grams, Y.Y. and Bouwstra, J.A. (2002) J. Control Release. 83, 253-262. 35
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