Pathway for skin penetration.ppt(1)
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  • *Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer
  • *Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer
  • Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs. experimental terminology. 9(3), 165-9.
  • Harry s cosmeticology (eighth edition ) page 352
  • *
  • Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2..(2008). Penetration mechanism of dimethyl sulfoxide in human and pig ear skin: An ATR–FTIR and near-FT Raman spectroscopic in vivo and in vitro study. 22(9). 405-417.
  • Mechanism of skin penetration-enhancing effect by laurocapram (the name of article)

Transcript

  • 1. GHAZWA SHAWASH بسم الله الرحمن الرحيم University Of Jordan
  • 2. Pathway For Skin Penetration
  • 3. What is skin components ?
  • 4.  
  • 5. What is penetration ?
    • Skin penetration is differs from skin permeation.
    • skin penetration is the former describes the passage of an ingredients into the skin ( we hope to the target skin layer).
    • Skin permeation is the passage of an ingredient through the skin to the circulatory system.
  • 6.
    • Interaction between a given compound and the skin is physicochemical in nature.
  • 7. what is the penetration pathway?
    • (Penetration between SC corenocytes is the pathway by witch most compounds penetrate the skin )
    • The intercellular pathway .*( 5%-30%of total area)
    • The intracellular pathway
    • 3. The intrafollicular pathway and the
    • sebaceous glands pathway
    • 4. The polar pathway .
  • 8. The intercellular pathway and the intracellular pathway
    • * Hydrophilic compounds may preferably partition into the intracellular domain
    • *lipophilic compound may cross the SC through the intercellular rout.
    • So the major pathway for a compound is highly dependent upon its partition coefficient.
  • 9. stratum corneum constituents 75%-80% protein , 5%-15% lipids , 5%-10% unidentified element
  • 10.
    • Skin can
    • absorb water
    • and the proof
    • is wrinkle of this finger
  • 11. The intrafollicular pathway and the sebaceous glands pathway
    • *(Mainly for lipid and surprisingly it is for a charge and large polar molecule) .
    • sebaceous gland on the total skin surface represent not more than 0.1% , but some time it will be the target such as acne
    • *Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer
  • 12. Follicle distribution
  • 13. The polar pathway
    • This route is believed to be hydrophilic in natural , it is composed of aqueous region surrounded by polar lipids that create the walls of microchannels.
  • 14. The polar pathway
    • The localization of the
    • hydrophilic pores is unclear,
    • but they think that :
    • 1- it is intercellular .
    • 2- it is intracellular keratin .
  • 15. The polar pathway
    • We need 3-10 corneocytes to create a columns that form a cluster.
    • Corneocytes edges inside each cluster were found to intercalate extensively , but neighboring cluster were separated by gaps of a few micrometers.
  • 16. The polar pathway
    • So know we will say that we have 2 different hydrophilic pathway :
    • 1- inter-cluster rout (within low penetration resistant)
    • 2- inter-coreocyte pathway (higher penetration resistance), it is twisted between coreocyte ,may be act as an actual channel in the skin.
  • 17. it is also thought to be the route by whitch water evaporates through the skin
  • 18. Factor Affecting Skin Penetration
    • 1- size of the molecule and MW.
    • 2- affinity of the molecule to the surface of the skin.
    • 3- compatibility with the intercellular lipids.
    • 4- the skin condition.
    • 5- the moisture content.
    • 6- tempreture .
    • 7- thickness of the SC.
    • 8- physical integrity.
  • 19. size of the molecule.
    • *smaller size more penetration.
    • *molecular weight (MW) of a
    • compound must be under 500
    • Dalton to allow skin absorption.
    • *Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical
    • compounds and drugs. experimental terminology. 9(3), 165-9.
  • 20. the skin condition
    • Scarred skin in Comparison to normal skin will be with no hair follicle and sebaceouse gland and thinning of the collagenouse fibers , penetration rate throw Scarred skin will be so less than normal skin .
  • 21. compatibility with the intercellular lipids
    • To do that we use Penetration enhancers witch is a substances that can partition into, and interact with, skin constituents .
  • 22. thickness of the SC
    • By increasing the thickness of the SC amount of water and lipid will increase and penetration of the skin increase. (sink condition)
    • My opinion
  • 23. The moisture content
    • As the amount of free moisture in the intercellular spaces increases the intercellular become larger and the amount of a substances penetrating the skin increase .
    • (the mechanism by witch hydration increase skin penetration is not will understood)
    • Harry s cosmeticology (eighth edition ) page 352
  • 24. tempreture
    • As the tempreture increases the penetration increase , because of :
    • 1- lowering of the activity coefficient of pharmaceutical substances in the skin.
    • 2- increases in drug solubility.
    • 3- increase in diffusion and blood flow .
    • 4- transition from gel to liquid crystal of layer lipid hydrocarbon chain will reduce the viscosity so increase the duffusion.
  • 25. Penetration Enhancer
    • There are more than one way to differentiate and classify skin penetration enhancer :
    • 1 - classifying them according to the preferred rout of penetration.
    • 2- according to carry different molecule .
    • 3 - according to their mechanism of enhancement.
  • 26. Penetration Enhancer according to the preferred rout of penetration
    • 1- solvent that enhance penetration through both polar and non-polar pathway.
    • 2- enhancers that preferentially affect the polar route .
    • 3- enhancer that mainly modify the non-polar route.
  • 27. Penetration Enhancer according to the preferred rout of penetration
    • 1- solvent that enhance penetration through both polar and non-polar pathway such as:
    • 2-pyrrolidone
    • b. N-methyl pyrrolidone
    • N-methyl-formaide
    • d. propylene glycol in combination with azon.
  • 28. Penetration Enhancer according to the preferred rout of penetration
    • 2- enhancer that mainly modify the non-polar route, such as :
    • propylene glycol and oleic acid.
    • propylene glycol alone.
  • 29. Penetration Enhancer according to the preferred rout of penetration
    • 3- enhancers that preferentially affect the polar route , such as:
    • a. Propylene glycol in combination with decylmethylsulfoxide.
  • 30. Penetration Enhancer according to the preferred rout of penetration
    • The 3 major mechanisms (polar) :
    • Extraction the SC lipids: (The permeability coefficient of polar molecule increased with increasing lipid extraction).
    • 2. Inducing a relaxation of the polymeric structure of the cytoplasmic matrix in keratinocytes cell.
    • 3. Changing the solvent properties of the SC. (surfactant)
  • 31. Penetration Enhancer according to the preferred rout of penetration
    • *Surfactant:
    • enhance transport of polar molecule by solubilization and removal of intercellular lipid and binding to keratin filament of the intracellular matrix , this resulted in cell order disruption .
    • non-ionic surfactant were shown to shows fluidizing effect on the SC.
  • 32. Penetration Enhancer according to their mechanism of enhancement.
    • 1- Enzyme .
    • 2- Chemical enhancers .
    • 3- Vesicular system .
    • 4- Ceramides (one of the lipid classes in the SC).
  • 33. (1) Enzyme
    • Using an enzyme to affect the barrier properties of the SC refer to either affecting activity of :
    • 1- enzyme present in the skin.
    • 2- Or to enzyme applied to it from outside.
  • 34. How dose the enzyme work ?
    • 1- by affecting the synthesis of lipid class in SC (fatty acid, cholesterol and ceramides), such as:
    • * 5-(tetradecyloxy)-2-furancarboxylic acid. this will prevent fatty acid synthesis.
    • * Fluvastatin .
    • this will prevent cholesterol synthesis .
  • 35. How dose the enzyme work ?
    • 2-by affecting metabolism and biochemical cascade in the skin , such as:
    • * papian ; is a proteolytic enzyme , that increase the SC thickness , and the living epiderm.
  • 36. How dose the enzyme work ?
    • 3- subtissues phase separation , lamellar bodies formation and created disorder in lamellar structures in the SC .
  • 37. (2) Chemical enhancers
    • Most chemical enhancers affect the intercellular lipid bilayers in the SC , it allows the creation of various types of (openings) in the bilayers.
    • Example:
    • * isopropyl myristate.
    • * isopropyl alcohol.
    • * oleic acid.
  • 38. Chemical enhancers
    • * oleic acid :
    • It was observed that oleic acid make alteration in the SC specifically in the intercellular spaces.
  • 39.
    • Another Chemical enhancers
  • 40. Penetration enhancers ( DMSO)
    • * Dimethyl sulfoxide (DMSO):
    • By changing in the conformation of the skin
    • Keratins from an α-helical to a β-sheet
    • Conformation ,that happen because of (DMSO
    • tended to bind to free water before the
    • protein-bound water was replaced and the
    • protein conformational changes were
    • induced.
  • 41. Penetration enhancers (azon)
    • Azone may act on the lipid-rich route because it fluidizes the stratum corneum lipids .
    • on the water-rich route because it enriches the water content .
    • The reason why Azone affects the skin permeation of a relatively broad spectrum of drugs may be that it affects at least two permeation routes in the skin barrier
  • 42. (3) Vesicular system
    • What is Vesicular system ?
    • It is an Encapsulation of the drug in vesicular structures such as liposomes .
  • 43. (3) Vesicular system
    • A major force driving vesicle penetration through the skin may be the water gradient across the epidermis.
  • 44. (3) Vesicular system
    • We have
    • * classic multi-layered phosphoplipid liposomes :
    • Act as a reservoir and would not be the carrier of choice.
    • * SC lipid-based liposomes :
    • were found to deliver a greater amount of the drug to the deep layer of the skin (epidermis and dermis) , the larger the mean size the poorer the penetration to SC layer.
  • 45. (3) Vesicular system
    • On the another hand the scientist found that :
    • *phospholipids liposomes increase SC lipid bilayer disorder and increase permeation .
    • *SC lipid-based liposomes have a high affinity to the SC and generate a reservoir because it increase the order of the lipid in the intercellular lamellae .
  • 46. (4) ceramides
  • 47. (4) ceramides
    • Ceramides in certain concentration were shown to create an imbalance in the intercellular lamellar organization and to enhance skin penetration .
    • In the study *they found that polar head of an enhancer is responsible for the penetration , and they found *that branched-chain alcohol have lower enhancement capability than the primary alcohol.
  • 48.
    • It is recommended to choose enhancers with different mechanisms of action , this will prevent competition at the site of action and has a better probability of not provoking irritation
  • 49. Summary
    • We talk a bout four of the skin penetration pathways ( the intercellular pathway ,the intracellular pathway, the intrafollicular pathway and the
    • sebaceous glands pathway, and the polar pathway ) and four types of penetration enhancer ( enzymes, chemical enhancer , and the vesicular system , ceramides )
  • 50. THE END
  • 51. References
    •  Cosmetic & toiletries magazine.(vol.120,No. 6/2005)
    •  Delivery System Handbook for Personal Care and Cosmetic Products. By Meyer
    •  Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs. experimental terminology. 9(3), 165-9.
    •  Harry s cosmeticology (eighth edition ) page 352
    •  Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2..(2008). Penetration mechanism of dimethyl sulfoxide in human and pig ear skin: An ATR–FTIR and near-FT Raman spectroscopic in vivo and in vitro study. 22(9). 405-417.
    •  Mechanism of skin penetration-enhancing effect by laurocapram (the name of article)