TDDS

1. By Amina M. Al.nema M.Sc. student Mosul University Pharmacy College

2. 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 contents 2

3. Transdermal drug delivery offers an attractive alternative to the oral administration and injection. Today about 74% of drugs are taken orally and are found not to be as effective as desired. Drug delivery through the skin (for systemic effect ) is commonly known as TDD and differs from traditional topical drug delivery. Introduction 3

4. also known popularly as ‘patches’. Transdermal patches: are dosage forms designed to deliver a therapeutically effective amount of drug from the outside of the skin through its layers into the blood stream. Introduction 4

5. advantages avoids the stomach environment ; no GI distress or other physiological contraindications 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 in place of a needle, then medical waste can also be , again, healthcare costs. 5

6. advantages 6. allows for the effective use of drugs with short biological half-lives ; 7. allows for the administration of drugs with narrow therapeutic windows ; 8. provides steady plasma levels of highly potent drugs; 9. TDDS, especially simple patches, are easy to use and noninvasive and patients like noninvasive therapies. 6

7. 7 Steady plasma level of Ethinyl estradiol / norelgestromin

8. disadvantages drugs that require high blood levels cannot be administered ; The adhesive used may not adhere well to all types of skin; drug or drug formulation may cause skin irritation or sensitization ; the patches can be uncomfortable to wear ; and this system may not be economical for some patients. 8

9. 9 Adverse events FDA (2005) announced that fentanyl td patches cause narcotic overdose and deaths Cause : manufacturing defect that allowed the gel containing the medication to leak out of its pouch too quickly, which could result in overdose and death. Improvement : use a matrix/adhesive suspension (where the medication is blended with the adhesive instead of held in a separate pouch with a porous membrane)

10. 10 Currently available drugs include:

11. Skin site for tdd The human skin is a readily accessible surface for drug  delivery.  Skin of an average adult body covers a surface of ~ 2 m ²  and receives about 1/3 of the  blood circulating through the body. Human skin comprises of three distinct but mutually dependent  layers : 11

12. Microscopically skin is a multilayered organ broadly composed of three tissue layers : The Epidermis The Dermis Subcutaneous fatty tissue. Skin anatomy 12

13. 13 Skin anatomy

14. 14 Hairy skin develops hair follicles and sebaceous glands The most important layer is the stratum corneum , or horny layer , which usually provides the rate-limiting or slowest step in the penetration process.

15. Transport mechanisms Principle mechanism is passive diffusion of drug through the skin. macro-routes may comprise: a.Transepidermal pathway b. Transfollicular pathway 15 Hair follicle Sebaceous gland Sweat gland

16. 16 Transport mechanisms

17. 17 Components of transdermal patches 1- Backing , 2- Drug, 3- Membrane, 4- Adhesive, 5- Liner.

18. 18 Generations of tdds Liquid reservoir system where the patch consists of a backing material that is both protective and adhesive,a liquid drug reservoir, a release membrane. 2. Adhesive matrix system where the adhesive and the drug are combined 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

19. 19 Estraderm® Androderm ® use the liquid-reservoir design Most currently available patches are the adhesive matrix design. Nicotine Patch 1st Generation

20. 20 Generations of tdds delivery of organic molecules by disrupting st . cor. barrier function by providing a driving force for the movement of molecules through the epidermis. This disruption should be reversible and avoid injury to the skin . Enhancement techniques are limited to small, lipophilic molecules and still have little effect on larger or hydrophilic molecules. 2nd Generation

21. 21 Enhancement techniques include: 1.chemical penetration enhancers, 2. gentle heating, 3. iontophoresis . 2nd Generation Generations of tdds

22. 22 1. Chemical Penetration Enhancers Methods for enhancing permeation in 2 nd g.tdds

23. 23 2. Heat as a penetration enhancer Methods for enhancing permeation in 2 nd g.tdds The use of heat to increase the permeability of the skin. One safe use of heat as a penetration enhancer is the Controlled Heat-Assisted Drug Delivery(CHADD) system. The lidocaine / tetracaine patch system.

24. 24 lidocaine / tetracaine patch

25. 25 The use of tiny electric current to promote flow of the drug (usually charged) through the skin. Methods for enhancing permeation in 2 nd g.tdds 3. Iontophoresis as a 2 nd G.penetration enhancer Iontophoresis is a powered drug delivery system that is indicated for the local administration of ionic drug solutions into the body for medical purposes and can be used as an alternative to injections .

26. 26 3. Iontophoresis as a 2 nd G.penetration enhancer Methods for enhancing permeation in 2 nd g.tdds

27. Self-contained, ultra-thin battery technology. Prepared by the clinician and applied to the patient in the clinic. With no external batteries or wires, patients are able to return to their daily activities while receiving time-released iontophoresis . A charged drug delivery electrode (negative) repels the drug ions into the underlying tissue. Wireless patch

28. 28 Generations of tdds 3rd Generation 3rd generation TDDS aim to severely disrupt the stratum corneum to allow large molecules to pass into the circulation.

29. 29 Human GnRH Methods for enhancing permeation in 3 rd g.tdds GnRH is not a small, organic compound but a somewhat larger oligopeptide . 1. Iontophoresis as a 3 rd G.penetration enhancer

30. GnRH Smart Patch® iontophoretic technology Quich , non-invasive, 10min. Application to skin. Methods for enhancing permeation in 3 rd g.tdds

31. 31 Methods for enhancing permeation in 3 rd g.tdds 2. Thermal ablation as a 3 rd G.penetration enhancer Thermal ablation technique seeks to severely disrupt the stratum corneum . 100s of degrees for very short periods of time (micro- to milliseconds) and forms painless, reversible microchannels in the stratum corneum without damaging the underlying tissue (2008).

32. 32 Methods for enhancing permeation in 3 rd g.tdds 3. Ultrasound as a penetration enhancer

33. 33 Methods for enhancing permeation in 3 rd g.tdds 3. Ultrasound as a penetration enhancer Ultrasound to Enhance Skin Permeability

34. 34 Microneedle array consists of chips. Used for adminstration of therapeutic proteins and vaccines. Methods for enhancing permeation in 3 rd g.tdds 4. Microneedle as a penetration enhancer 200-750 microns in length 150-650 microneedles /cm2

35. 35 Methods for enhancing permeation in 3 rd g.tdds 4. Microneedle as a penetration enhancer Poke and patch Method

36. 36 Methods for enhancing permeation in 3 rd g.tdds 4. Microneedle as a penetration enhancer Hollow micro needle array

37. 37 Intanza ® is a seasonal flu vaccine that has been approved in Europe since 2009. 4. Microneedle as a penetration enhancer Methods for enhancing permeation in 3 rd g.tdds

38. 38 Transdermal drug delivery technologies are becoming one of the fastest growing sectors within the pharmaceutical industry. Despite some disadvantages, transdermal drug delivery offers many advantages capable of improving patient health and quality of life. 1st and 2nd generation TDDS offer these advantages but are limited in the scope of molecules delivered through the skin. Conclusion

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