This document discusses the history and generations of transdermal drug delivery systems (TDDS). It describes 1st generation TDDS which use liquid reservoirs or adhesive matrices to deliver small, lipophilic drugs. 2nd generation systems use techniques like chemical enhancers, heat, or iontophoresis to increase skin permeability for small molecules. Recent 3rd generation techniques disrupt the skin barrier more extensively through iontophoresis, thermal ablation, ultrasound, or microneedle arrays to deliver larger or hydrophilic drugs like peptides. Transdermal delivery offers benefits over oral or injection routes but continuing innovation is needed to expand the types of drugs that can be delivered through the skin.

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

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.

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.

5. 1. avoids the stomach environment;
2. 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.

6. 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.

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

9.  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)

11. oThe human skin is a readily accessible surface for
drug delivery.
oSkin of an average adult body
covers a surface of ~ 2 m² and
receives about 1/3 of the
blood circulating through
the body.
oHuman skin comprises of three
distinct but mutually dependent
layers :

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

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

17. 1- Backing,
2- Drug,
3- Membrane,
4- Adhesive,
5- Liner.

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

20.  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. Enhancement techniques include:
1.chemical penetration enhancers,
2. gentle heating,
3. iontophoresis.
2nd Generation

22. 1. Chemical Penetration Enhancers

23. 2. Heat as a penetration enhancer
 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. lidocaine/tetracaine patch

25. The use of tiny electric current to promote flow
of the drug (usually charged) through the skin.
3. Iontophoresis as a 2nd 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. 3. Iontophoresis as a 2nd G.penetration enhancer

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.

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

29. Human GnRH
GnRH is not a small, organic compound but a somewhat
larger oligopeptide.
1. Iontophoresis as a 3rd G.penetration enhancer

30. GnRH Smart Patch® iontophoretic technology
Quich, non-invasive, 10min. Application to skin.

31. 2. Thermal ablation as a 3rd 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. 3. Ultrasound as a penetration enhancer

33. 3. Ultrasound as a penetration enhancer
Ultrasound to Enhance Skin Permeability

34.  Microneedle array consists of chips.
 Used for adminstration of therapeutic proteins and
vaccines.
4. Microneedle as a penetration enhancer
200-750 microns in length
150-650 microneedles/cm2

35. 4. Microneedle as a penetration enhancer
Poke and patch Method

36. 4. Microneedle as a penetration enhancer
Hollow micro needle array

37. Intanza® is a seasonal flu
vaccine that has been
approved in Europe since
2009.
4. Microneedle as a penetration enhancer

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.