Penetration enhancer with their examples

Helpful to understand the overview of mechanism of enhancing the skin penetration with their examples.

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Flow of Presentation
Introduction
DrugDeliveryRoutesAcrossHumanSkin
PropertiesForIdealPenetrationEnhancers
UsesofPenetrationEnhancers
MeritsAndDemeritsofPenetrationEnhancers
ClassificationofPenetrationEnhancers
PhysicalEnhancers
References
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3. INTRODUCTION
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Penetrationenhancers:
Substancesusedtoincreasepermeationofskinmucosa.
Increasestheabsorptionofpenetrantthroughtheskin.
Synonyms:absorptionpromoterandsorptionaccelerants.
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4. Permeationoccurbydiffusionvia
1.Transdermalpermeationthroughthe
stratumcorneum
2.Intercellularpermeationthroughstratum
corneum
3.Transappendagedpermeationvia
a.hairfollicle
b.sebaceousglands
c.sweatglands
DRUG DELIVERY ROUTES ACROSS HUMAN SKIN
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Actions of penetration enhancers within the intercellular lipid domain
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6. DESIRABLE PROPERTIES FOR IDEAL PENETRATION ENHANCERS
Non-toxic,non-irritatingandnon-allergic
Rapidworking
Predictableandreproducibledurationofaction
Nopharmacologicalactivitywithinthebody
Workunidirectionally
Whenremovedfromtheskin,barrierpropertiesshouldreturnbothrapidlyandfully
Compatiblewithbothexcipientsanddrugs
Cosmeticallyacceptable
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7. 1.Toincreasethedeliveryofionisabledrugs.Example:timololmaleateetc
2.Todelivertheimpermeabledrugs.Example:heparinetc
3.Tomaintainlevelofdrugintobloodstream
4.Toimprovetheefficacyoflesspotentdrugswithhigherdose.Example:
oxymorphane
5.Todeliverthedrugshavinghighmolecularweightlikepeptideandhormones
6.Todecreaselagtimeoftransdermaldrugdeliverysystem
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USES OF PENETRATION ENHANCERS
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Merits of Penetration Enhancers
1)Mostdrugspenetrateatratessufficientlyhighfortherapeuticefficiencyby
usingpenetrationenhancers
2)Itisusefulforunabsorbabledrugstofacilitatetheirabsorptionthroughskin
3)Itcanimprovetransdermalabsorptionoftopicalpreparation
4)Noadverseeffectonskin
5)Donotaffectzeroorderskinpermeationprofileofskin
6)Theterpeneslikelimoneneinpropyleneglycolsolutionareeffective
penetrationenhancerforcytotoxicdrugs
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1.Theeffectiveconcentrationvariesfromdrugtodrug
2.Theusesofdifferentpenetrationenhancerwithvariousconcentrationsare
restrictedcompletely
3.Physicochemicalpropertiesofenhancersarealsoaffectingthesideeffectsin
thebody
Demerits of Penetration Enhancers
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PENETRATION
ENHANCERS
Chemical
enhancers
Physical
enhancers
Drug vehicle
based
Natural
penetration
Miscellaneous
Biochemical
approach
CLASSIFICATION

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Mechanismofaction:
1.Bydistruptionofhighlyorderedstructureofstratumcorneumlipid
2.Byinteractionwithintercellularprotein
3.Byimprovedpartitionofthedrugorsolventintostratumcorneum
Examples:
Sulfoxide-DMSO,DMF,DMAC
Azones
Surfaceactiveagents-SLS,BKC
Amines&amides-urea
Fattyacidsetc
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Mechanismofaction:
Interaction of enhancers with stratum corneum and development of SAR for
enhances with optimal characteristics and minimal toxicity.
Examples Ion pairs and complex Coacervates chemical potential adjustment.
Drug selection.
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1.Terpenes-
Menthol, Linalool,
Limonene,Carvacrol
2.Essentialoil-
Basiloil,Neemoil,
Eucalyptusoil
Mechanismofaction:
Itmayincreaseoneormoreoffollowingeffects
1.Partitioncoefficient
2.Diffusioncoefficient
3.LipidExtraction
4.DrugSolubility
5.MacroscopicBarrierPerturbation
6.MolecularOrientationofTerpenesMolecule
withLipidBilayer
Examples
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1.Iontophoresis
•Iontophoresisisdefinedas“theapplicationofasmallelectriccurrent(0.5
mA/cm
2
orless)withalowvoltage,todriveionicandpolarmolecules
acrosstheskinandintothetissues”
•Usedtodelivermoleculessuchasneutralandchargedmolecules,lowand
highmolecularweightdrugsnamelyphenobarbital,ranitidineand
zidovudine
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Iontophoresis
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2. Microneedle Array
MNarraysarecomposedofmultiplemicron-
sizedprojectionswhicharetypicallyassembled
ononesideofasupportingbaseorpatch
Length-25μmto2000μm
Thereforetheycancreatelittleholesinthe
stratumcorneumwithoutpainandbecomethe
effectivewaytoenhancethedeliveryof
therapeuticmoleculesandmacromolecules
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3. Sonophoresis
Synonyms-PhonophoresisorUltrasound
Itinvolvestheuseofultrasonicenergyto
enhanceskinpenetrationofactivesubstances
Frequencyrange-20KHzto100KHz
e.g.Drugsgivenaretetracycline,biomycin
andpenicillinforskindiseases
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4. Magnetophoresis
Actsasanexternaldrivingforcetoenhancedrugdeliveryacrosstheskin
Inducesalterationintheskinstructurethatcouldcontributetoanincreasein
permeability
e.g.Magnatoliposomesconsistingofmagneticparticleswrappedin
phospholipidbilayerwhichareappliedfordrugdelivery,Magneticresonance
imagingmarkersforcancerdiagnosis
Mechanismofaction:
Drug delivery across the membrane by the application of magnetic field
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5. Electroporation
•Itinvolvestheapplicationofshort,high
voltagepulsestoskin
•Skinelectroporation,alsocalled
electropermeabilization,createstransient
aqueousporesinthelipidbyapplicationof
highvoltageofelectricalpulsesof
approximately100–1000V/Cmforshort
time(milliseconds)
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6. Thermophoresis
Thermalenergywhenappliedtoskin,causeincreasedskin
permeability
Heatingduringtopicalapplicationofadrugdilatespenetration
pathwayintheskinandincreasekineticenergyandmovementof
particlesinthetreatedareawhichfacilitatesdrugabsorption
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7. Radiofrequency
Itinvolvesexposureoftheskintoahighfrequencyalternatingcurrentof100
KHzthatresultintheformationofheat-inducedmicrochannelsinthecell
membrane.
Rateofdrugdeliveryiscontrolledbynumberanddepthofmicrochannels
formedwhichdependsonthepropertiesofmicroelectrodesincontactwiththe
skinduringtreatment.
e.g.Skindeliveryoftestosteroneandgrowthhormones.
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•Permeabilityvariesaccordingtoskincondition
•Hydratedskinismorepermeablethandryskin
•Hydrationofskinreducesresistancebylooseningthe
packagingoflayersofstratumcorneum
8. Hydration of stratum corneum
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Chemicalpeels-forsuperficialorlight(epidermal),medium(epidermal–dermal
junction)ordeep(deeppapillaryorpapillaryreticulardermis)treatments
Microdermabrasionwhichusesastreamofaluminiumoxidecrystals
Dermabrasionwhichemploysamotor-drivenabrasivefraiseorcylinder
Laserablationapplieshigh-poweredpulsestovapouriseasectionofthehornylayer
Adhesivetape-Toremovestratumcorneumpriortodrugapplication
Amicroinfusordevice-Todeliverpeptides,proteinsandothermacromolecules
9. Stripping of stratum corneum
Asthehornylayerusuallyprovidesthepermeationbarrier,for
efficientdrugdeliveryitcanberemovedbyfollowingtechniques:
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26. 1)Maghrabya, G. M. M. E., Michael, C., Barrie, C. F., 2005. International Journal of
Pharmaceutics305, 90–104
2)Barry, B. W., 2001. European Journal of Pharmaceutical Sciences14, 101 –114
3)Karande, P., JainA., Ergun, K., Kispersky, V., Mitragotri, S., 2005. PNAS102(13), 4688–
4693
4)Williams, A. C., Barry, B. W., 2012. Advanced Drug Delivery Reviews64, 128–137
5)Gill, H.S., Prausnitz, M. R., 2007. Journal of Control Drug Release117, 227–37
6)Henry, S., McAllister, D.V., Allen, M.G., Prausnitz, M. R., 1998. Journal of
Pharmaceutical Sciences87, 922–925
7)Saini, S., Baghel, S., Agrawal, S. S., 2014. Journal of Advanced Pharmacy Education &
Research 4(1), 31-40
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References
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