Transdermal Drug Delivery

System
A transdermal patch or skin patch is
a medicated adhesive patch that is
placed on the skin to deliver a
specific dose of medication through
the skin and into the bloodstream

Advantages of transdermal
patches

Topical patches are a painless, noninvasive way to

deliver substances directly into the body.
Topical patches are a better way to deliver substances
that are broken down by the stomach acids, not wellabsorbed from the gut, or extensively degraded by the
liver.
Topical patches over a controlled, steady delivery of
medication over long periods of time.
Topical patches have fewer side effects than oral
medications or supplements.
Topical patches are easier to use and remember.
Topical patches over an alternative to people who
cannot, or prefer not to take medications or supplements
orally. Topical patches are cost-effective

Limitation
TDDS cannot deliver ionic drugs.
TDDS cannot achieve high drug levels in
blood/plasma.
It cannot develop for drugs of large
molecular size.
TDDS cannot deliver drugs in a pulsatile
fashion.
TDDS cannot develop if drug or
formulation causes irritation to skin.

Conditions in which Transdermal

patches are used
When the patient has intolerable side effects
(including constipation) and who is unable to take
oral medication (dysphagia) and is requesting an
alternative method of drug delivery.
Where the pain control might be improved by
reliable administration. This might be useful in
patients with cognitive impairment or those who for
other reasons are not able to self-medicate with
their analgesia.
It can be used in combination with other
enhancement strategies to produce synergistic
effects.

Conditions in which Transdermal

patches are not used
Cure for acute pain is required.
Where rapid dose titration is
required.
Where requirement of dose is equal
to or less than 30 mg/24 hrs.

Factors affecting transdermal

bioavaibility
Stratum corneum layer of the skin
Anatomic site of application on the body
(3) Skin condition and disease
Age of the patient
Skin metabolism
Desquamation (peeling or flaking of the
surface of the skin)
Skin irritation and sensitization
Race

Formulation factors include

Physical chemistry of transport
Vehicles and membrane used
Penetration enhancers used

Mechanism of Drug release

Patch
The
application
of
the
transdermal patch and the flow of
the active drug constituent from the
patch to the circulatory system via
skin occur through various methods

1. Iontophoresis
Iontophoresis
passes
a
few
milliamperes of current to a few
square centimeters of skin through
the electrode placed in contact with
the formulation, which facilitates
drug delivery across the barrier.
Mainly used of pilocarpine delivery to
induce sweating as part of cystic
fibrosis diagnostic test. Iontophoretic
delivery of lidocaine appears to be a

Basic Principle of
Iontophoresis

2. Electroporation
Electroporation is a method of application of
short, high-voltage electrical pulses to the skin.
After electroporation, the permeability of the
skin for diffusion of drugs is increased by 4
orders of magnitude. The electrical pulses are
believed to form transient aqueous pores in the
stratum corneum, through which drug transport
occurs. It is safe and the electrical pulses can
be administered painlessly using closely
spaced electrodes to constrain the electric field
within the nerve-free stratum corneum.

3. Application by ultrasound
Application of ultrasound, particularly
low frequency ultrasound, has been
shown to enhance transdermal
transport of various drugs including
macromolecules. It is also known as
sonophoresis.

3. Application by ultrasound

4. Use of microscopic
projection
The first ever patents for drug delivery for
percutaneous administration of drug was based
on this method. These microneedles of length 50110 micrometre will penetrate SC and epidermis
to deliver drug. When pressed into the skin, the
arrays make microscopic punctures that are large
enough to deliver macromolecules, but small
enough that the patient does not feel the
penetration or pain. The drug is surface coated on
the microneedles to aid in rapid absorption. They
are used in development of cutaneous vaccines
for tetanus and influenza.

Magnetophoresis
It involves application of magnetic
field that acts as an external driving
force to enhance the diffusion of a
diamagnetic solute across the skin.
Skin exposure to a magnetic field
might
also
induce
structural
alterations that could contribute to
an increase in permeability

Types of Transdermal
Patches
Single-layer drug-in-adhesive: In
this type the adhesive layer contains
the drug. The adhesive layer not only
serves to adhere the various layers
together and also responsible for the
releasing the drug to the skin. The
adhesive layer is surrounded by a
temporary liner and a backing

Multi -layer drug in adhesive

This type is also similar to the single
layer but it contains a immediate
drug release layer and other layer
will be a controlled release along
with
the
adhesive
layer.
The
adhesive layer is responsible for the
releasing of the drug. This patch also
has a temporary liner-layer and a
permanent backing.

Multi -layer drug in adhesive

This type is also similar to the single
layer but it contains a immediate
drug release layer and other layer
will be a controlled release along
with
the
adhesive
layer.
The
adhesive layer is responsible for the
releasing of the drug. This patch also
has a temporary liner-layer and a
permanent backing.

Vapor patch
In this type of patch the role of adhesive
layer not only serves to adhere the
various layers together but also serves as
release vapour. The vapor patches are
new to the market, commonly used for
releasing of essential oils in decongestion.
Various other types of vapor patches are
also available in the market which are
used to improve the quality of sleep and
reduces the cigarette smoking conditions.

Reservoir system
In this system the drug reservoir is embedded
between an impervious backing layer and a
rate controlling membrane. The drug releases
only through the rate controlling membrane,
which can be micro porous or non porous. In
the drug reservoir compartment, the drug can
be in the form of a solution, suspension, gel or
dispersed in a solid polymer matrix.
Hypoallergenic adhesive polymer can be
applied as outer surface polymeric membrane
which is compatible with drug

Matrix system
i.Drug-in-adhesive system
In this type the drug reservoir is formed
by dispersing the drug in an adhesive
polymer
and
then
spreading
the
medicated adhesive polymer by solvent
casting or melting (in the case of hot-melt
adhesives) on an impervious backing
layer. On top of the reservoir, unmediated
adhesive polymer layers are applied for
protection purpose.

Matrix system
ii. Matrix-dispersion system
In this type the drug is dispersed
homogenously in a hydrophilic or lipophilic
polymer matrix. This drug containing polymer
disk is fixed on to an occlusive base plate in a
compartment
fabricated
from
a
drug
impermeable backing layer. Instead of
applying the adhesive on the face of the drug
reservoir, it is spread along with the
circumference to form a strip of adhesive rim.

Basic components of TDDS

The common ingredients which are used for the preparation of
TDDS
are as follows

1. Liners: Protects the patch during storage. Ex: polyester film

2. Adhesive: Serves to adhere the patch to the skin for
systemic delivery of drug. Ex: Acrylates, Polyisobutylene,
Silicones.
3. Permeation enhancers: Controls the Release of the drug. Ex:
Terpenes, Terpenoids, Pyrrolidones. Solvents like alcohol,
Ethanol, Methanol. Surfactants like Sodium Lauryl sulfate,
Pluronic F127, Pluronic F68
4. Backing layer: Protect patch from outer environment. Ex:
Cellulose derivatives, poly vinyl alcohol, Polypropylene Silicon
rubber

Considerations for polymer

selection in transdermal delivery
system:

Should be stable and non-reactive with the drug moiety.

Easily available, fabricated and manufactured in to
desired formulations.
The properties of polymer e.g. molecular weight glass
transition temp. melting point and chemical
functionality etc. should be such that drug can easily
diffused through it and with other components of
system.
Mechanical properties should not change if large
amount of drug incorporate.
Should provide consistent release of drug throughout
the life of system

Suitable Drug Candidates for TDDS

Various
physicochemical,
pharmacokinetic
and
pharmacological properties of the drug should be
considered for transdermal system development. Because
of the limited permeability of the skin, drugs have to be
transdermally delivered by passive diffusion through the
skin, and are limited by several substantial constraints.
The drug moiety for transdermal system should be potent
( dose in mg),
having molecular weight 1000 Da,
adequate solubility in the vehicle, logP value of 5,
melting point of 200 C and appropriate lipophilicity,
undergo extensive pre-systemic metabolism,
non-ionic and non-irritant are considered as suitable
candidates for delivery via this route

Commonly used polymers for TDDS

Natural Polymers: e.g. gelatin cellulose
derivatives, gums, natural rubber, shellac,
waxes and chitosan etc.
Synthetic Elastomers: e.g., hydrin rubber,
polyisobutylene, polybutadiene, silicon rubber,
nitrile, , neoprene, butylrubber, acrylonitrile etc
Synthetic Polymers: e.g. polyvinylchloride,
polyethylene,polyvinyl alcohol, polypropylene,
polyamide, polyacrylate, polyurea,
polyvinylpyrrolidone,polymethylmethacrylateetc

Applications of polymers in
TDDS
Polymers used in transdermal system in versatile manner such
as:
Rate controlling membrane: It control the release of drug by
disperse through an inert polymer matrix. The polymer powder
blended with drug moiety by physical manner and then moulded
in to desired shape with required thickness and surface area.
Adhesive: make an intimate contact between the skin and
transdermal system. It carries the drug which is dissolved or
dispersed in solution or suspension form. The quality of drug
diffused in to skin depending on the holding power..
Pressure sensitive adhesive: Hitherto the rapidity of
transdermal system can be done by pressure sensitive adhesive.
The three most commonly usedadhesives are polyisobutylene,
polyacrylate and silicones in TDD devices

Penetration Enhancers
Penetration enhancers: Compounds which
promote the penetration of topically applied
drugs are commonly referred as absorption
promoters,
accelerants,
or
penetration
enhancers.
Penetration
enhancers
are
incorporated into a formulation to improve the
diffusivity and solubility of drugs through the
skin that would reversibly reduce the barrier
resistance of the skin. Thus allow the drug to
penetrate to the viable tissues and enter the
systemic circulation

Desired Properties of penetration

enhancers
It should be non-irritant, non-sensitizing, nonphototoxic, and non-comedogenic
Onset of action should be rapid and duration of activity should be predictable
and reproducible.
iii. Have no pharmacological activity in the body i.e. should not bind to the
receptor site.
iv. Upon removal of the enhancer, the upper layer should immediately and fully
recover its normal barrier property.
v. The barrier function of the skin should reduce in one direction only .
Endogenous material should not be lost to the environment by diffusion out of
the skin.
vi. The accelerants should be chemically and physically compatible with all
drugs and adjuvants to be formulated in topical preparations and devices.
vii. It should be inexpensive, tasteless and colorless,
viii. It should readily formulated in to dermatological preparations.
ix. It should have a desired solubility parameter that approximates that of skin.
x. It should adhere and spread well on the skin with a suitable skin feel.

Methods of Preparation of
patches
Circular teflon mould method

Solutions containing polymers in various ratios are used in an

organic solvent.
Calculated amount of drug is dissolved in half the quantity of
same organic solvent. Enhancers in different concentrations
are dissolved in the other half of the organic solvent and then
added.
Di-N-butylphthalate is added as a plasticizer into drug polymer
solution. The total contents are to be stirred for 12 hrs and
then poured into a circular teflon mould.
The moulds are to be placed on a leveled surface and covered
with inverted funnel to control solvent vaporization in a laminar
flow hood model with an air speed of 0.5 m/s. The solvent is
allowed to evaporate for 24 hrs.
The dried films are to be stored for another 24 hrs at 250.5C
in a desiccators containing silica gel before evaluation to
eliminate aging effects.

Methods of Preparation of
patches
Mercury substrate method
In this method drug is dissolved in polymer
solution along with plasticizer.
The above solution is to be stirred for 10- 15
minutes to produce a homogenous dispersion
and poured in to a leveled mercury surface,
covered with inverted funnel to control
solvent
evaporation. substrate method

Methods of Preparation of
patches
By using IPM membranes method
In this method drug is dispersed in a mixture of water
and propylene glycol containing carbomer 940 polymer and
stirred for 12 hrs in magnetic stirrer. The dispersion is to be
neutralized and made viscous by the addition of
triethanolamine. Buffer pH 7.4 can be used in order to
obtain solution gel, if the drug solubility in aqueous
solution is very poor. The formed gel will be incorporated in
the IPM membrane

Methods of Preparation of
patches
By using EVAC membranes method
In order to prepare the target transdermal therapeutic
system, 1% carbopol reservoir gel, polyethelene (PE),
ethylene vinyl acetate copolymer (EVAC) membranes can
be used as rate control membranes. If the drug is not
soluble in water, propylene glycol is used for the
preparation of gel. Drug is dissolved in propylene glycol,
carbopol resin will be added to the above solution and
neutralized by using 5% w/w sodium hydroxide solution. The
drug (in gel form) is placed on a sheet of backing layer
covering the specified area. A rate controlling membrane
will be placed over the gel and the edges will be sealed by
heat to obtain a leak proof device

Methods of Preparation of
patches
Aluminium backed adhesive film method
Transdermal drug delivery system may produce
unstable matrices if the loading dose is greater
than 10 mg. Aluminium backed adhesive film
method is a suitable one. For preparation of same,
chloroform is choice of solvent, because most of
the drugs as well as adhesive are soluble in
chloroform. The drug is dissolved in chloroform and
adhesive material will be added to the drug
solution and dissolved. A custammade aluminium
former is lined with aluminium foil and the ends
blanked off with tightly fitting cork block