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Transdermal drug delivery system was presented to overcome the difficulties of drug delivery especially oral route. A transdermal 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. It promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of delivery system such as oral, topical, i.v., i.m., etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier, as a result, only medications whose molecules are small can easily penetrate the skin, so it can be delivered by this method. This review article describes the overall introduction of transdermal patches including type of transdermal patches, method of preparation of transdermal patches and factor affecting etc.
Oral route is the most popular route of drug delivery system but it has some disadvantages including first pass metabolism, drug degradation etc in gastrointestinal tract due to enzymes, pH etc. To overcome these problems, a novel drug delivery system was developed by Chien in 1992, Banker in 1990, Guy in 1996. It was Transdermal patches or Transdermal delivery system. In this system medicated adhesive patches are prepared which deliver therapeutically effective amount of drug across the skin when it placed on skin. They are available in different sizes & having more than one ingredient. Once they apply on unbroken skin they deliver active ingredients into systemic circulation passing via skin barriers. A transdermal patch containing high dose of drug inside which is retained on the skin for prolonged period of time, which get enters into blood flow via diffusion process.
Drug can penetrate through skin via three pathways-
a) Through hair follicals.
b) Through sebaceous glands
c) Through sweat duct.
Transdermal drug delivery systems are used in various skin disorders, also in the management of angina pectoris, pains, smoking cessation & neurological disorders such as Parkinson’s disease [1,2].
Single-layer Drug-in-Adhesive System: In this type of patch the adhesive layer of this system contains the drug. The adhesive layer not only serves to adhere the various layers together, along with the entire system to the skin, but it is also responsible for the releasing the drug. The adhesive layer is surrounded by a temporary liner and a backing (Figure 1).
Reservoir System: In this System the drug reservoir is kept in between backing layer and a rate controlling membrane. And drug releases through microporous rate controlled membrane. Drug can be in the form of a solution, suspension,or gel or dispersed in a solid polymer matrix in the reservoir
Matrix System: This system is of Two type
a) Drug-in-Adhesive System: For the formation of drug
reservoir, the drug dispersed in an adhesive polymer and
then spreading the medicated polymer adhesive by solvent
casting or by melting the adhesive (in the case of hot-melt
adhesives) on to an impervious backing layer.
b) Matrix-Dispersion System: In this system the drug
is dispersed homogeneously in a hydrophilic or lipophilic
polymer matrix. And this containing polymer along with
drug is fixed onto an occlusive base plate in a compartment
fabricated from a drug- impermeable backing layer. In this
system the adhesive is spread along the circumference
instead of applying on the face of drug reservoir to form a
strip of adhesive rim .
Micro-Reservoir System: This system is a combination
of reservoir and matrix- dispersion systems. In which drug is
suspended in an aqueous solution of water-soluble polymer
and then dispersing the solution homogeneously in a lipophilic
polymer to form thousands of unleachable, microscopic spheres
of drug reservoirs .
g) Other excipients like plasticizers and solvents .
Polymer Matrix/ Drug Reservoir: It is prepared by
dispersing the drug in liquid or solid state synthetic polymer base.
It should have biocompatibility and chemical compatibility with
the drug and other components of the system such as penetration
enhancers. Additionally they should provide consistent and
effective delivery of a drug throughout the product’s intended
shelf life and should be of safe status. Polymers used in
Transdermal drug delivery systems are classified as
a) Natural Polymers: e.g. cellulose derivatives, zein,
gelatin, shellac, waxes, gums, natural rubber and chitosan
b) Synthetic Elastomers: e.g. polybutadiene, hydrin
rubber, silicon rubber, polyisobutylene, acrylonitrile,
neoprene, butyl rubber etc.
c) Synthetic Polymers: e.g. polyvinylalcohol,
polyvinylchloride, polyethylene, polypropylene,
polyacrylate, polyamide, polyurea, polyvinylpyrrolidone,
polymethylmethacrylate etc [6,7].
Drugs: Some of ideal properties of drug & some factors to
be consider during preparation of Transdermal patches are as
Permeation Enhancers: The chemical compounds that
enhance the permeability of stratum corneum so as to attain
therapeutic levels of the drug candidate. They improve the
permeability by interacting with Stratum corneum.
a) Ideal Properties of Permeation Enhancers
i. They should be non-irritating, non-toxic & non- allergic
ii. They should not bind to receptor site i.e. not showing
any pharmacological activity.
iii. They should be cosmetically acceptable with an
appropriate skin feel. 
Pressure Sensitive Adhesive (PSA): It helps to increase the
adherence of transdermal patch to the skin surface. It can easily
remove from the smooth surface without leaving a residue on it.
c) silicon based adhesives
Backing Laminate: It is a supportive material which is
impermeable to drugs and also to permeation enhancers. They
should chemically compatible with the drug, enhancer, adhesive
and other excipients.
Ex: Vinyl, Polyethylene and Polyester films .
Release Liner: This is the primary packaging material that
can protect the patch during application. It is made up of base
layer which may be
a) Non-occlusive (e.g. paper fabric)
b) Occlusive (e.g. polyethylene, polyvinylchloride)
It is made up of silicon or Teflon. Release liner should be
chemically inert & it should be permeable to drug, penetration
enhancers & water.
Asymmetric TPX Membrane Method: This method was
discovered by Berner and John in 1994. By this method prototype
patch can be prepared by using heat sealable polyester film
(type 1009, 3m) with a concave of 1cm diameter as the backing
membrane. Drug dispersed on concave membrane, covered by
a TPX [poly (4-methyl-1- pentene)] asymmetric membrane, and
sealed by an adhesive.
a) Preparation: These are prepared by using the dry or
wet inversion process. In this TPX is dissolved in a mixture
of solvent (cyclohexane) and non- solvent additives at 60°C
to form a polymer solution. The polymer solution is kept at
40°C for 24 hrs and cast on a glass plate. Then casting film
is evaporated at 50°C for 30 sec, then the glass plate is to
be immersed immediately in coagulation bath (temperature
mantained at 25°C). After 10 minutes of immersion, the
membrane can be removed, air dry in a circulation oven at
50°C for 12 hrs.
Circular Teflon Mould Method: It was discovered by Baker
and Heller in 1989. Polymeric solution in various proportions is
used as an organic solvent. Then that solution is divided in two
parts. In one parts calculated amount of drug is dissolved & in
another part enhancers in different concentration are dissolved,
and then two parts mixed together. Then plasticizer (e.g., Di-Nbutylphthalate)
is added into the 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 levelled
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 h. After which
a dried film formed & that is to be stored for another 24 h at
25±0.5°C in a desiccators containing silica gel before evaluation
to eliminate aging effects.
Mercury Substrate Method: In this method drug &
plasticizer get dissolved in polymeric solution. It stirred for 10-
15 min to produce homogenous dispersion then it is poured into
levelled mercury surface, covered with inverted funnel to control
By Using “IPM Membranes” Method: In the mixture of
water & polymer (propylene glycol containing Carbomer 940
polymer) drug get dispersed and stirred for 12 hrs in magnetic
stirrer. The dispersion is to be neutralized and made viscous by
the addition of triethanolamine. If the drug solubility in aqueous
solution is very poor then solution gel is obtained by using
Buffer pH 7.4. The formed gel will be incorporated in the IPM
By Using “EVAC Membranes” Method: For the preparation
of TDS, 1% carbopol reservoir gel, polyethelene (PE), ethylene
vinyl acetate copolymer (EVAC) membrane is needed as rate
control membrane. If the drug is insoluble in water then use
propylene glycol for gel preparation. 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.
Preparation of TDDS by Using Proliposomes: By carrier
method using film deposition technique proliposomes are
prepared. Drug and lecithin ratio should be 0.1:2.0 taken as an
optimized one from previous references. For the preparation of
proliosome in 100ml round bottom flask take 5mg of mannitol
powder, then it is kept at 60-70°c temperature and the flask
is rotated at 80-90 rpm and dried the mannitol at vacuum for
30 minutes. After drying, the temperature of the water bath is
adjusted to 20- 30°C. Drug and lecithin are dissolved in a suitable
organic solvent mixture, a 0.5ml aliquot of the organic solution is
introduced into the round bottomed flask at 37°C, after complete
drying second aliquots (0.5ml) of the solution is to be added. After
the last loading, the flask containing proliposomes are connected
in a lyophilizer and subsequently drug loaded mannitol powders
(proliposomes) are placed in a desiccator overnight and then
sieved through 100 mesh. The collected powder is transferred
into a glass bottle and stored at the freeze temperature until
By using Free Film Method: In this process firstly cellulose
acetate free film is prepared by casting it on mercury surface.
And 2% w/w polymer solution is prepared by using chloroform.
Plasticizers are to be added at a concentration of 40% w/w
of polymer weight. Then 5 ml of polymer solution is poured
in a glass ring which is placed over the mercury surface in a
glass petridish. The rate of evaporation of the solvent can be
controlled by placing an inverted funnel over the petridish.
The film formation is noted by observing the mercury surface
after complete evaporation of the solvent. The dry film will be
separated out and stored between the sheets of wax paper in a
desiccator until use. By this process we can prepare free films of
different thickness can be prepared by changing the volume of
the polymer solution [11,12].
Future aspects in Drug delivery system include liposomes,
Niosomes and micro emulsion. Aim of this development is to
improve delivery of drug that has low inherent solubility in most
of classical formulation excipients. A wide range of potential drugs
for delivery like steroids, antifungal, antibacterial, interferon,
methotrexate, local anesthetics are formulated. The market for
transdermal patches has been estimated to increase in future and
has recently experienced annual growth of at rate of 25%. This
figure will increase in future as novel devices emerge and list of
marketed transdermal drug increases. Transdermal delivery of
analgesics is likely to continue to increase in popularity as there
are further improvements in design. Research is being performed
to increase safety and efficacy. To improve practical matters such
as the experience for the wearer of the patch, and also to provide
more precise drug delivery associated with increased duration
of action. Other potential improvements include improved
transdermal technology that utilizes mechanical energy to
increase drug flux across the skin either by altering the skin
barrier or increasing the energy of the drug molecules. After the
successful design of patches using iontophoresis, various modes
of ‘active’ transdermal technologies are being investigated for
different drugs. These include electroporation (short electrical
pulses of high voltage to create transient aqueous pores in the
skin), sonophoresis (uses low frequency ultrasonic energy to
disrupt the stratum corneum), and thermal energy (uses heat
to make the skin more permeable and to increase the energy of
drug molecules). Magnetic energy, magnetophoresis, has been
investigated as a means to increase drug flux across the skin. The
transdermal patch may be an underutilized tool for management
of acute and chronic pain. With improved delivery and a wider
range of analgesics, we expect the popularity and applicability
of this modality to deliver drugs to increase. In current scenario,
transdermal route of drug delivery system in comparison with
oral treatment as the most successful innovative research area in
new drug delivery system, with around 40% of the drug delivery
candidate products under clinical trails related to transdermal or
dermal system. The transdermal drug delivery systems (TDDS)
have been designed as an alternative, safest and easy route for
systemic drug delivery. The systemic drug administration though
skin holds several advantages such as maintenance constant
drug level in blood plasma, less number of side effects, and
improvement of bio availability by circumvention of hepatic first
pass metabolism and increase patient compliance with respect to
drug regime used for treatment. In recent times, skin considered
as a safest port for drug administration, to provide continuous
drug release into systemic circulation .