Introduction, advantages & disadvantages . Skin : site of drug delivery. Skin Anatomy , transport mechanisms. Components of transdermal patches. Generations of TDDS. Recent Methods for enhancing permeation of TDDS
Transdermal drug delivery offers an attractivealternative to the oral administration and injection. Today about 74% of drugs are taken orally andare found not to be as effective as desired.Drug delivery through the skin(for systemic effect ) is commonlyknown as TDD and differs fromtraditional topical drug delivery.
also known popularly as ‘patches’.Transdermal patches: are dosage forms designedto deliver a therapeutically effective amount ofdrug from the outside of the skin through itslayers into the blood stream.
1. avoids the stomach environment;2. no GI distress or other physiologicalcontraindications of the oral route exist;3. easy to use, patches can compliance &medical costs;4. avoids the first-pass effect;5. If a transdermal delivery system is used inplace of a needle, then medical waste canalso be , again, healthcare costs.
6. allows for the effective use of drugs with shortbiological half-lives;7. allows for the administration of drugs withnarrow therapeutic windows;8. provides steady plasma levels of highly potentdrugs;9. TDDS, especially simple patches, are easyto use and noninvasive and patients likenoninvasive therapies.
1. drugs that require high blood levels cannot beadministered;2. The adhesive used may not adhere well to alltypes of skin;3. drug or drug formulation may cause skinirritation or sensitization;4. the patches can be uncomfortable to wear;5. and this system may not be economical forsome patients.
FDA (2005) announced that fentanyl td patches causenarcotic overdose and deathsCause: manufacturing defect that allowed the gelcontaining the medication to leak out of its pouch tooquickly, which could result in overdose and death.Improvement : use a matrix/adhesivesuspension (where the medication isblended with the adhesive instead ofheld in a separate pouch with a porousmembrane)
oThe human skin is a readily accessible surface fordrug delivery.oSkin of an average adult bodycovers a surface of ~ 2 m² andreceives about 1/3 of theblood circulating throughthe body.oHuman skin comprises of threedistinct but mutually dependentlayers :
Microscopically skin is a multilayered organ broadly composed ofthree tissue layers : The Epidermis The Dermis Subcutaneous fatty tissue.
Hairy skin develops hairfollicles and sebaceous glandsThe most important layer is thestratum corneum, or horny layer,which usually provides the rate-limiting or slowest step in thepenetration process.
Principle mechanism is passive diffusion of drugthrough the skin. macro-routes may comprise:a.Transepidermal pathway b. Transfollicular pathwayHair follicleSebaceousgland Sweat gland
1. Liquid reservoir system where the patch consists of a backing materialthat is both protective and adhesive,a liquid drug reservoir, a releasemembrane.2. Adhesive matrix system where the adhesive and the drug arecombined in the same layer leaving only three layers to the patch;the backing layer, the drug and adhesive layer, and the protective layer.1st Generation
Estraderm®Androderm®use the liquid-reservoirdesignMost currently available patches are theadhesive matrix design.1st Generation
delivery of organic molecules by disrupting st.cor. barrier function by providing a driving force forthe movement of molecules through the epidermis. This disruption should be reversible and avoidinjury to the skin.Enhancement techniques are limited tosmall, lipophilic molecules and still have little effecton larger or hydrophilic molecules.2nd Generation
2. Heat as a penetration enhancer The use of heat to increase the permeability of theskin.One safe use of heat as a penetration enhancer is theControlled Heat-Assisted Drug Delivery(CHADD)system.The lidocaine/tetracaine patch system.
The use of tiny electric current to promote flowof the drug (usually charged) through the skin.3. Iontophoresis as a 2nd G.penetration enhancerIontophoresis is a powered drugdelivery system that is indicated forthe local administration of ionicdrug solutions into the body formedical purposes and can be usedas an alternative to injections.
3. Iontophoresis as a 2nd G.penetration enhancer
Self-contained, ultra-thin battery technology. Prepared by the clinician and applied to the patient in theclinic. With no external batteries or wires, patients areable to return to their daily activities whilereceiving time-released iontophoresis.A chargeddrug deliveryelectrode(negative)repels thedrug ionsinto theunderlyingtissue.
3rd Generation3rd generationTDDS aim toseverely disrupt thestratum corneum toallow largemolecules to passinto the circulation.
Human GnRHGnRH is not a small, organic compound but a somewhatlarger oligopeptide.1. Iontophoresis as a 3rd G.penetration enhancer
2. Thermal ablation as a 3rd G.penetration enhancerThermal ablation technique seeks to severely disrupt thestratum corneum.100s of degrees for very short periods of time (micro- tomilliseconds) and forms painless, reversible microchannels inthe stratum corneum without damaging the underlying tissue(2008).
3. Ultrasound as a penetration enhancerUltrasound to Enhance Skin Permeability
Microneedle array consists of chips. Used for adminstration of therapeutic proteins andvaccines.4. Microneedle as a penetration enhancer200-750 microns in length150-650 microneedles/cm2
4. Microneedle as a penetration enhancerPoke and patch Method
4. Microneedle as a penetration enhancerHollow micro needle array
Intanza® is a seasonal fluvaccine that has beenapproved in Europe since2009.4. Microneedle as a penetration enhancer
Transdermal drug delivery technologies arebecoming one of the fastest growing sectors withinthe pharmaceutical industry.Despite some disadvantages, transdermaldrug delivery offers many advantages capableof improving patient health and quality of life. 1st and 2nd generation TDDSoffer these advantages but arelimited in the scope of moleculesdelivered through the skin.