 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

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 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.
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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.

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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. 5
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.
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7
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.
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 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
9
membrane)
10
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 : 11
Microscopically skin is a multilayered organ broadly composed of
three tissue layers :
 The Epidermis
 The Dermis
 Subcutaneous fatty tissue.

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13
 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 14
penetration process.
Principle mechanism is passive diffusion of drug
through the skin. macro-routes may comprise:
a.Transepidermal pathway b. Transfollicular pathway

Sebaceous
gland Sweat
gland

Hair follicle

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16
1- Backing,

2- Drug,

3- Membrane,

4- Adhesive,

5- Liner. 17
 1st Generation

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; 18
the backing layer, the drug and adhesive layer, and the protective layer.
1st Generation
Estraderm®
Androderm®
use the liquid-reservoir
design

Most currently available patches are the

adhesive matrix design.

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 2nd Generation

 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. 20
2nd Generation

Enhancement techniques include:

1.chemical penetration enhancers,
2. gentle heating,
3. iontophoresis.

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1. Chemical Penetration Enhancers

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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.

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lidocaine/tetracaine patch

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3. Iontophoresis as a 2nd G.penetration enhancer

The use of tiny electric current to promote

flow of the drug (usually charged) through
the skin.

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
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injections.
3. Iontophoresis as a 2nd G.penetration enhancer

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 A charged
drug
delivery
electrode
(negative)
repels the
drug ions
into the
underlying
tissue.

 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.
3rd Generation

3rd generation
TDDS aim to
severely disrupt
the stratum
corneum to allow
large molecules to
pass into the
circulation. 28
1. Iontophoresis as a 3rd G.penetration enhancer

GnRH is not a small, organic compound but a somewhat

larger oligopeptide.

29

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

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3. Ultrasound as a penetration enhancer

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3. Ultrasound as a penetration enhancer

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Ultrasound to Enhance Skin Permeability

4. Microneedle as a penetration enhancer

 Microneedle array consists of chips.

 Usedfor adminstration of therapeutic proteins and

vaccines.
200-750 microns in length
150-650 microneedles/cm2

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4. Microneedle as a penetration enhancer

Poke and patch Method

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4. Microneedle as a penetration enhancer

Hollow micro needle array

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4. Microneedle as a penetration enhancer

Intanza® is a seasonal flu

vaccine that has been
approved in Europe since
2009.

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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 38

delivered through the skin.

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