Transdermal Drug Delivery System1

TRANSDERMAL DRUG DELIVERY SYSTEM
Introduction:-
Transdermal patch of scopolamine is the first transdermal patch which

is approved by FDA in 1981. Transdermal delivery systems of
scopolamine is used for the prevention of motion sickness
(TransdermScop, ALZA Corp.) and nitro-glycerine for the prevention of
angina pectoris associated with coronary artery disease (Transderm
Nitro). Transdermal drug delivery products give therapeutic benefit to
patients. Approximately 16 active ingredients and more than 35
Transdermal drug delivery products have been approved for use
globally and for sale in the US respectively. In the year 2005 market of
$ 12.7 billion is found by statistics analysis that is expected to increase
to $ 21.5 billion in the year 2011 and $31.5 billion in the year 2015.
Transdermal drug delivery systems (TDDS), also known as patches,
are dosage forms designed to deliver a therapeutically effective
amount of drug across a patients skin. In order to deliver therapeutic
agents through the human skin for systemic effects, the
comprehensive morphological, biophysical and physicochemical
properties of the skin are to be considered. Transdermal delivery
provides a leading edge over injectables and oral routes by increasing
patient compliance and avoiding first pass metabolism respectively 1 .
Transdermal delivery not only provides controlled, constant
administration of the drug, but also allows continuous input of drugs
with short biological half-lives and eliminates pulsed entry into
systemic circulation, which often causes undesirable side effects. Thus
various forms of Novel drug delivery system such as Transdermal drug
delivery systems, Controlled release systems, Transmucosal delivery
systems etc. emerged. Several important advantages of transdermal
drug delivery are limitation of hepatic first pass metabolism,
enhancement of therapeutic efficiency and maintenance of steady
plasma level of the drug. The first Transdermal system, TransdermSCOP was approved by FDA in 1979 for the prevention of nausea and
vomiting associated with travel, particularly by sea. The evidence of
percutaneous drug absorption may be found through measurable blood
levels of the drug, detectable excretion of the drug and its metabolites
in the urine and through the clinical response of the patient to the
administered drug therapy.
Since the beginning of life on the earth, humans have applied a lot of
substances to their skin as cosmetics and therapeutic agents.
However, it was the twentieth century when the skin became used as
route for long term drug delivery.Today about two third of drugs
(available in market) are taken orally, but these are not as effective as
required. To improve upon the features the transdermal drug delivery
system was emerged.Amongst all techniques which were used for
SRMSCET (PHARMACY) BAREILLY
release drugs in a controlled way into the human body, transdermal

drug delivery system (TDDS) is widely recognized as one of the most
reliable, appealing as well as effective technique. Delivery of drugs
through the skin has been an attractive as well as a challenging area
for research. Over the last two decades, transdermal drug delivery had
become an appealing and patience acceptance technology as it is
minimize and avoids the limitations allied with conventional as well as
parenteral route of drug administration such as peak and valley
phenomenon i.e. exhibit fluctuation in plasma drug concentration level,
pain and inconvenience of injections; and the limited controlled release
options of both.
A transdermal patch is defined as medicated adhesive patch which is
placed above the skin to deliver a specific dose of medication through
the skin with a predetermined rate of release to reach into the
bloodstream. Today the most common transdermal system present in
the market mainly based on semi permeable membranes which were
called as patches.
Transdermal drug delivery system is defined as the topically
administered medications in the form of patches which when applied to
the skin deliver the drug, through the skin at a predetermined and
controlled rate. Transdermal patches are delivered the drug through the
skin in controlled and predetermined manner in order to increase the
therapeutic efficacy of drug and reduced side effect of drug. Controlled
drug release can be achieved by transdermal drug delivery systems
(TDDS) which can deliver the drug via the skin portal to systemic
circulation at a predetermined rate over a prolonged period of time.1
For effective Transdermal drug delivery system, the drug are easily able
to peneterate the skin and easily reach the target site. TDDS increase
the patient compliance and reduces the load as compared to oral route.
FDA approved the first Transdermal system Transderm-SCOP in 1979.
FDA approved this for the prevention of nausea and vomiting associated
with ravel, particularly by sea.2 Transdermal therapeutic systems are
also defined as a self contained, discrete dosage forms which, when
applied to the intact skin, deliver the drug, through the skin at control
rate to the systemic circulation. Transdermal formulation maintain drug
concentration within the therapeutic window for prolong period of time
ensuring that drug levels neither fall below the minimum effective
concentration nor exceed the maximum effective concentration.
The common ingredients which are used for the preparation of TDDS
are as follows:1.Drug:- Drug is in direct contact with release liner.Ex: Nicotine,
Methotrexate and Estrogen.
2.Liners:- Protects the patch during storage. Ex: polyester film.
3.Adhesive:- Serves to adhere the patch to the skin for systemic
delivery of drug. Ex: Acrylates, Polyisobutylene, Silicones.

4.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.
5.Backing layer:- Protect patch from outer environment. Ex:
Cellulose derivatives, poly vinyl alcohol, Polypropylene Silicon rubber.
TYPES OF TRANSDERMAL PATCHES

a) 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.
b) 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.
c) Vapour 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 vapour 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.
d) 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 ratecontrolling
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.
e) 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.
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.
f) Microreservoir system: In this type the drug delivery system is

a combination of reservoir and matrix-dispersion system. The drug
reservoir is formed by first suspending the drug in an aqueous
solution of water soluble polymer and then dispersing the solution
homogeneously in a lipophilic polymer to form thousands of
unreachable, microscopic spheres of drug reservoirs. This thermodynamically
unstable dispersion is stabilized quickly by immediately cross-linking the polymer in
situ by using cross linking agents.
VARIOUS METHODS FOR PREPARATION TDDS:a.
Asymmetric TPX membrane method:- A prototype patch

can be fabricated for this a heat sealable polyester film (type 1009,
3m) with a concave of 1cm diameter will be used as the backing
membrane. Drug sample is dispensed into the concave membrane,
covered by a TPX {poly(4-methyl-1-pentene)}asymmetric membrane,
and sealed by an adhesive.
b. 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-Nbutylphthalate 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.
The type films are to be evaluated within one week of their
preparation.
C. 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.
d.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.
e.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.
f.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 blocks.
g.Preparation of TDDS by using Proliposomes:- The

proliposomes are prepared by carrier method using film deposition
technique. From the earlier reference drug and lecithin in the ratio of
0.1:2.0 can be used as an optimized one. The proliposomes are
prepared by taking 5mg of mannitol powder in a 100 ml round bottom
flask which is kept at 60-70c 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 20-30C. 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 37C, 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
over night and then sieved through 100 mesh. The collected powder is
transferred into a glass bottle and stored at the freeze temperature
until characterization.
h.By using free film method:- Free film of cellulose acetate is

prepared by casting on mercury surface. A polymer solution 2% w/w is
to be prepared by using chloroform. Plasticizers are to be incorporated
at a concentration of 40% w/w of polymer weight. Five ml of polymer
solution was poured in a glass ring which is placed over the mercury
surface in a glass petri dish. The rate of evaporation of the solvent is
controlled by placing an inverted funnel over the petri dish. 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. Free
films of different thickness can be prepared by changing the volume of
the polymer solution.
IDEAL PROPERTIES OF TDDS

The ideal properties of Transdermal drug delivery
system are:-
Optimum partition coefficient required for the therapeutic action of

drug.
Shelf life upto 2 years.
Low melting point of the drug is desired which is less than 200oC
Patch size should be <40cm2.
The pH of the saturated solution should be between 5-9.
S.No.
1
2
3
4
5
Properties
Self life
Particle size
Dose frequency
Aesthetic appeal
Packaging
Skin reaction
comment
Up to 2 yrs
<40cm2
Once in a day or once in a week
Clear or white colour
Easy removal of release liner
and min.
no. of steps required to apply
Non irritating and non
6
Advantages of Transdermal drug delivery system:Avoidance of first pass metabolism of drugs.

Transdermal medication delivers a steady infusion of a drug over a
prolonged period of time. Adverse effects or therapeutic failures
frequently associated with intermittent dosing can also be avoided.
The simplified medication regimen leads to improved patient
compliance and reduced the side effects, inter and intra-patient
variability.
No interference with gastric and intestinal fluids.
Maintains stable or constant and controlled blood levels for longer
period of time.
Comparable characteristics with interavenous infusion.
It increases the therapeutic value of many drugs via avoiding specific
problems associated with the drug like GI irritation, lower absorption,
decomposition due to hepatic first pass effect.
This route is suitable for the administration of drugs having very
short half life, narrow therapeutic window and poor oral availability.
Improved patient compliance and comfort via non-invasive, painless
and simple application..
Flexibility of terminating the drug administration by simply removing
the patch from the skin.
Self administration is possible in these system.
Disadvantages of Transdermal drug delivery system:The possibility of local irritation may develop at the site of
application. Many problems like Erythema, itching, and local edema
can be caused by the drug, the adhesive, or other excipients in the
patch formulation.
Drugs has large molecular size makes absorption difficulty. So drug
molecule should ideally be below 800-1000 daltons
.
Many drugs with a hydrophilic structure having a low peneteration
through the skin and slowly to be of therapeutic benefit. Drugs with a
lipophillic character, however, are better suited for transdermal
delivery.
The barrier function of the skin changes from one site to another on
the same person, from person to person and with age.
FACTORS AFFECTING TRANSDERMAL DRUG DELIVERY

Biological factors
Physiological factors
Skin condition
Temperature and pH
Skin age
Diffusion coefficient
Blood flow
Drug concentration
Regional skin site
Skin hydration
Species Differences
Partition coefficient
Molecular size and shape
SYSTEM:-
Layers of skin:- Three major layers of the skin are

Epidermis. Dermis. Hypodermis.
SKIN :-Structure of Skin The human skin is a mutilayered organ

composed of many histological layers. Skin is most accessible organ in
body. Its major functions are; protection of major or vital internal
organs from the external influences, temperature regulations, control
of water output and sensation. The skin of an average adult body
covers approximately surface area of two square meters and receives
about one-third of the blood circulating through the body. Skin is the
complex organ and allows the passage of various chemicals into and
across the skin. Skin serves as the point of administration for
systemically active drugs, the drug applied topically will be absorbed,
first into the systemic circulation and then transported to target tissue
Epidermis:-The epidermis is a stratified, squamous, keratinizing

epithelium. The keratinocytes comprise the major cellular component
(> 90%) and the responsible for the evolution of barrier function.
Keratinocytes change their shape, size and physical properties when
migrating to the skin surface. Other cells present which are present in
this layer include Melanocytes, Langerhans cells and Markel cells, none
of which appears to contribute to the physical aspects of the barrier.
Microscopically, the epidermis further divided into five anatomical
layers with stratum corneum forming the outer most layer of the
epidermis, exposing to the external environment. Stratum corneum is
the outermost layer of epidermis approximately 100-150 micrometers
thick, has no blood flow. This is the layer most important to
transdermal delivery as its composition allows it to keep water within
the body and foreign substances out. Beneath the epidermis, the
dermis contains the system of capillaries that transport blood
throughout the body. If the drug is able to penetrate the stratum
corneum, then it can enter the blood stream. A process known as
passive diffusion, which occurs too slowly, is the only means to transfer
normal drug across the layer.
Dermis:-The dermis is the inner and larger (90%) skin layer,

comprises primarily of connective tissue and provides supports to the
epidermis layer of the skin. The boundary between dermis and
epidermis layer is called Dermal- Epidermal junction which provides a
physical barrier for the large molecules of drug and cells. The dermis
incorporates blood and lymphatic vesicles and nerve endings. The
extensive microvasculature network which is found in the dermis
represents the site of resorption for drugs absorbed across the
epidermis. The dermis can be divided into two anatomical region;
papillary dermis and reticular dermis. Papillary is the thinner outermost
portion of the dermis. Collagen and elastin fibres are mostly vertically
oriented in the papillary region and connected with the dermalepidermal junction. In reticular dermis, fibres are horizontally oriented.
As skin is major factor for the determination of various drug delivery
aspects like permeation and absorption of drug across the dermis.
Hypodermis:- The hypodermis is the adipose tissue layer which is

found in between of dermis and aponeurosis and fasciae of the
muscles. The subcutaneous adipose tissue is structurally and
functionally are well integrated with the dermis through the nerve and
vascular networks. The hypodermis layer is composed of loose
connective tissues and its thickness varies according to the surface of
body. promote the penetration of topically applied drugs are commonly
referred to as accelerants, absorption promoters, or penetration
enhancers. Chemical enhancers act by increasing the drug
permeability through the skin by causing reversible damage to the
stratum corneum and by increasing the partition coefficient of the drug
to promote its release from the vehicle into the skin.
Aim and Project

Need for the study:- Transdermal Drug Delivery System is the
system in which the delivery of the active ingredients of the drug
occurs through the skin. Transdermal drug delivery system can improve
the therapeutic efficacy and safety of the drugs because drug delivered
through the skin at a predetermined and controlled rate. Skin is the
important site of drug application for both the local and systemic
effects. Skin of an average adult body covers a surface of
approximately 2 m2 and receives about one-third of the blood
circulating through the body. Skin is an effective medium from which
absorption of the drug takes place and enters the circulatory system.
Various types of Transdermal patches are used that delivered the
specific dose of medication directly into the blood stream. This review
article covers a brief outline of the trasdermal drug delivery system,
advantages over conventional drug delivery system, Layers of the skin,
various components of transdermal patch, penetration enhancers, and
evaluation of transdermal system and applications of Transdermal
patch.Transdermal patches are pharmaceutical preparation of varying
sizes, containing, one or more active ingredient, intended to be applied
to the unbroken skin in order to deliver the active ingredient to the
systemic circulation after passing through the skin barriers, and it avoid
first pass effect. Transdermal patches delivers the drugs for systemic
effects at a predetermined and controlled rate. Through a diffusion
process, the drug enters the bloodstream directly though the skin. Since
there is high concentration on the patch and low concentration in the
blood, the drug will keep diffusing into the blood, the drug will keep
diffusing into the blood for a long period of time, maintaining the
constant concentration of drug in the blood flow. Characterization of
transdermal patch is use to check its quality, size, time of onset &
duration, adhesive property, thickness, weight of patch, moisture of
content, uniformity & cutaneous toxicological studies. The market for
transdermal products has been in a significant upward trend that is
likely to continue for the foreseeable future. An increasing number of
TDD products continue to deliver real therapeutic benefit to patients
around the world. More than 35 TDD products have now been approved
for sale in the US, and approximately 16 active ingredients are
approved for use in TDD products globally.
10
Literature Review
Mark R. Prausnitz,.et al.,(2000):- The past twenty five years
have seen an explosion in the creation and discovery of new medicinal
agents. Related innovations in drug delivery systems have not only
enabled the successful implementation of many of these novel
pharmaceuticals, but have also permitted the development of new
medical treatments with existing drugs. The creation of transdermal
delivery systems has been one of the most important of these
innovations, offering a number of advantages over the oral route. In
this article, we discuss the already significant impact this field has
made on the administration of various pharmaceuticals,explore
limitations of the current technology; and discuss methods under
exploration for overcoming these limitations and the challenges ahead.
Pfister WR,.et al.,(1990):- Part I of this article reviews the

classification, chemistry, properties, selection, and use of skin
permeation enhancers in transdermal drug delivery systems and
dermal patches. The authors discuss ideal properties of enhancers and
describe various enhancers' actions on the skin. Part II will describe
interactions between permeation enhancers and other transdermal
delivery system components, such as backing materials,pressuresensitive adhesives, membranes, and release liners. Adhesive
properties critical to the optimization of a transdermal formulation will
be discussed.
Jonathan Hadgraft,.et al.,(1999):- The skin has an extremely

good barrier function and to improve topical bioavailability it is usually
necessary to employ enhancement strategies. Optimization of the
applied formulation can improve release to the skin and the use of
supersaturation achieves this objective. However, supersaturated
states are inherently unstable. High solvent concentrations in the
formulation may remove skin lipids reducing the barrier function of the
stratum corneum.
Jain Amit.k,.et al,.(2008):- Third-generation delivery systems

target their effects to skins barrier layer of stratum corneum using
11
microneedles, thermal ablation, microdermabrasion, electroporation

and cavitational ultrasound. Microneedles and thermal ablation are
currently progressing through clinical trials for delivery of
macromolecules and vaccines, such as insulin, parathyroid hormone
and influenza vaccine
Robert Langer,.et al.,(2003):- Transdermal delivery represents

an attractive alternative to oral delivery of drugs and is poised to
provide an alternative to hypodermic injection too 14. For thousands of
years, people have placed substances on the skin for therapeutic
effects and, in the modern era, a variety of topical formulations have
been developed to treat local indications. The first transdermal system
for systemic deliverya three-day patch that delivers scopolamine to
treat motion sicknesswas approved for use in the United States in
1979.
Heather A.E. Benson:- 1987There is considerable interest in the

skin as a site of drug application both for local and systemic effect.
However, the skin, in particular the stratum corneum, poses a
formidable barrier to drug penetration thereby limiting topical and
transdermal bioavailability. Skin penetration enhancement techniques
have been developed to improve bioavailability and increase the range
of drugs for which topical and transdermal delivery is a viable option.
This review describes enhancement techniques based on drug/vehicle
optimisation such as drug selection, prodrugs and ion-pairs,
supersaturated drug solutions, eutectic systems, complexation,
liposomes, vesicles and particles. Enhancement via modification of the
stratum corneum by hydration, chemical enhancers acting on the
structure of the stratum corneum lipids and keratin, partitioning and
solubility effects are also discussed. The mechanism of action of
penetration enhancers and retarders and their potential for clinical
application is described
P.M.Patil,.et al,.(2012):- Drug delivery system relates to the

production of a drug, its delivery medium, and the way of
administration. Drug delivery systems are even used for administering
nitroglycerin. Transdermal drug delivery system is the system in which
the delivery of the active ingredients of the drug occurs by the means
of skin.
Nikhil Sharma,.et al.,(2011):- There has been little change in the

composition of the patch systems. Modifications have been mostly
limited to refinements of the materials used. The present review article
12
explores the overall study on transdermal drug delivery system (TDDS)

which leads to novel drug delivery system (NDDS).
Kumar, J. Ashok,.et al.,(2004):- Today about 74% of drugs are

taken orally and are found not to be as effective as desired. To improve
such characters transdermal drug delivery system was emerged. Drug
delivery through the skin to achieve a systemic effect of a drug is
commonly known as transdermal drug delivery and differs from
traditional topical drug delivery. Transdermal drug delivery systems
(TDDS) are dosage forms involves drug transport to viable epidermal
and or dermal tissues of the skin for local therapeutic effect while a
very major fraction of drug is transported into the systemic blood
circulation.
Ghosh P.The,.et al., (2016 ):Navigating sticky areas in transdermal product development
benefit of transdermal delivery over the oral route to combat
such issues of low bioavailability and limited controlled release
opportunities are well known and have been previously discussed
by many in the field (Prausnitz et al., 2004 Prausnitz et al. (2004)
Hadgraft and Lane, 2006 Hadgraft and Lane (2006) However,
significant challenges faced by developers as a product moves from
the purely theoretical to commercial production have hampered full
capitalization of the dosage forms vast benefits. While different
technical aspects of transdermal system development have been
discussed at various industry meetings and scientific workshops,
uncertainties have persisted regarding the pharmaceutical
industry's conventionally accepted approach for the development
and manufacturing of transdermal systems.
Anubhav Arora,.et al.,(2014):- Skin makes an excellent site for

drug and vaccine delivery due to easy accessibility, immunosurveillance functions avoidance of macromolecular degradation in the
gastrointestinal tract and possibility of self-administration. However,
macromolecular drug delivery across the skin is primarily accomplished
using hypodermic needles, which have several disadvantages including
accidental needle-sticks, pain and needle phobia. These limitations
have led to extensive research and development of alternative
methods for drug and vaccine delivery across the skin. This review
focuses on the recent trends and developments in this field of microscale devices for transdermal macromolecular delivery.
13
Ptel J Houk,.et al.,(1999):- The mechanism of action of

penetration enhancers and retarders and their potential for clinical
application is described Transdermal drug delivery system is the
system in which the delivery of the active ingredients of the drug
occurs by the means of skin.
K.Alvin,.et al.,(2006):- This review describes enhancement

techniques based on drug/vehicle optimisation such as drug selection,
prodrugs and ion-pairs, supersaturated drug solutions, eutectic
systems, complexation, liposomes, vesicles and particles. ideal
properties of enhancers and describe various enhancers' actions on the
skin. Part II will describe interactions between permeation enhancers
and other transdermal delivery system components, such as backing
materials.
John S Lumin,.et al.,(1998):- Optimization of the applied
formulation can improve release to the skin and the use of
supersaturation achieves this objective. However, supersaturated
states are inherently unstable The creation of transdermal delivery
systems has been one of the most important of these effect.
Materials And Method
Advances in synthetic materials and patch design have led to
transdermal drug patches that are more esthetically acceptable
and that are capable of delivering sustained dosing of active
compounds for several days in a small package.Growth in
demand for drug patches is being driven by several factors factors with strong demographic and population trend
underpinnings. Further improvements to transdermal transport
and the introduction of new patch designs will keep this segment
expanding through 2020.Important materials markets for
transdermal patches include patch backing layers, release liners,
matrix materials and membranes. As patch designs expand to
accommodate the need for higher drug loads in smaller
packages, the role of specialty materials will remain a key design
factor.
In vitro method
Excised skin
Artificial membrane
Release methods
without a rate
Limiting membrane
In vivo method
Histology, Surface loss, Micro
dialysis
Analysis of blood tissue or fluid
Observation of pharmacological or
physiological response
Physical properties of skin,
Bioassays
14
SKIN AS A SITE FOR DRUG INFUSION:The skin is the largest organ of the body. The skin an average adult
body is about 20 square feet and it received about one third of total
available blood. The skin is multilayered organ composed of three
histological tissue: the outermost layer of skin,epidermis is which provides a waterproof
barrier and creates our skin tone.
dermis, beneath epidermis, contains tough connective tissue, hair
follicles, and sweat glands and deeper subcutaneous tissue
(hypodermis) is made of fat and connective tissue.
1. Transcellular/Intracellular permeation through the stratum corneum
2. Intercellular permeation through the stratum corneum
3. Transappendageal permeation via the hair follicles, sweat and
sebaceous glan.,
Mechanism of transdermal permeation:Transdermal permeation of a drug moiety involves the following steps:
i. Sorption by stratum corneum
ii. Permeation of drug through viable epidermis
iii. Uptake of the drug moiety by the capillary network in the dermal
papillary layer
iv. The drug must possess some physicochemical properties to reach
target site via systemically through stratum corneum
The rate of permeation of drug moiety across the skin is governed by
following equation:Ps( Cd Cr)
Where, Cd= concentration of penetrate in the donor phase on the
surface of skin Cr = concentration of penetrate in the receptor phase
body.
15
Fig.7. Different route of skin penetration

A constant rate of drug permeation achieved, if Cd >Cr then
the equation reduced as:dQ/dT=Ps.Cd
the rate of skin permeation (dQ/dt) becomes a constant, if the Cvalue
remains fairly constantthroughout the course of skin permeation
Tomaintain the Cdat a constant value, it is critical tomake the drug to
be released at a rate (Rr) which is always greater than the rate of skin
uptake. By doing so, the drug concentration on the skin surface (Cd) is
maintained at a level which is always greater than the equilibrium (or
saturation) solubilityof the drug in the stratum corneum and maximum
rate of skin permeation.
Apparently, the magnitude of (dQ/do)mis determined by the skin
permeability coefficient (Ps) of the drugand its equilibrium solubility in
the stratum conium(Ces).
Basic components of transdermal system:Polymer matrix or matrices:- Polymers are the foundation of
transdermal system. The selection of polymer and design are of prime
importance.
16
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 transtition
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.
The polymers used in transdermal system are:Natural Polymers:- e.g. zein, 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, ,polymethyl
methacrylate etc.
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 skinand
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 arepolyisobutylene,
polyacrylate and silicones in TDD Devices.
17
Release liners:- The patch is covered by protective liner during

storage until it is used .The release liner removed and discarded just
before the application of patch over the skin since release liner is in
intimate contact with the transdermal system hence it should be
physically as well as chemically inert. The release liner is composed
of a base layer which may be non-occlusive (e.g. paper fabric) or
occlusive (e.g. polyethylene, polyvinylchloride) and a release
coating layer made up of silicon or Teflon. Other materials used as
release liner in transdermal patches include polyester foil and
metalized laminate.
Backing laminate:-While design the baking layer following
points must be in consideration:
Must be flexible.
Having low water vapour transmission rate so as to promote skin
hydration and thus greater skin permeability of drug
Should be compatible with transdermal system as remain in use
while applying.
Should be chemical resistance.
Having good tensile strength.
Non irritant
Examples of backings laminate are polyethylene film, polyester film,
and polyolefin film, and aluminumvapor coated layer.
Drug:-Transdermal delivery of drugs has taken a surge ofpopularity

nowadays. Various physicochemical,pharmacokinetic and
pharmacological properties of the drugshould 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 adequate solubility in the
vehicle, logP value of 5, melting point of 200 C and appropriate
lipophilicity, undergo
extensive presystemic metabolism, non-ionic and non-irritant
areconsidered as suitable candidates for delivery via this route.
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.
18
Desired properties for penetration enhancers:i. It should be non-irritant, non-sensitizing, nonphototoxic, and non
comedogenic.
ii. Onset of action should be rapid and duration of activity should be
predectible 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 colourless,
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.Some of the examples of the widely used classical
enhancersinvolve various classes that include water,
hydrocarbonsalcohols, acids amines, amides, esters, surfactant
terpenes,terpenoidsand essential oil, sulfoxides, lipids
andmiscellaneous such as cyclodextrin derivatives, chitosan etc.
Other excipients:Plasticizers:-Palsticizers have also been used in many formulations

ranging from 5 to 20% (w/w, dry basis). Along with the brittleness and
ductility of the film, it is also responsible for adhesiveness of the film
with other surfaces or membranes and improvement in strength of
film. Some of its examples are glycerol or sorbitol, at 15%,w/w, dry
basis, phosphate, phthalate esters, fatty acid esters and glycol
derivatives such as PEG 200, and PEG 400.
Solvents:-Various solvents such as methanol, chloroform, acetone,

isopropanol and dichloromethane etc. are used to prepare drug
reservoir.
19
Approaches in the
therapeutic system:-
development
of
transdermal
Several technologies have been successfully developed to provide a

rate control over the release and the transdermal permeation of drugs.
These technologies are as follows:1.Adhesive dispersion type system:- The system consists of
drug-impermeable backing membrane, the drug reservoir which is
prepared by directly dispersing the drug in an adhesive polymer and
then spreading the medicated adhesive by solvent casting or hot
melting onto a flat sheet of drug-impermeable backing to form a thin
drug reservoir layer. On top of this, a layer of rate-controlling adhesive
polymer( non-medicated) of constant thickness is spread to produce an
adhesive diffusion-controlled drug delivery system with detachable
release liner which in an ideal situation is removed and the patch is
applied to the skin for a required period of time. Illustration of this type
of system is exemplied by development and marketing of transdermal
therapeutic system of angina pectoris and Valsartan as angiotensin II
type 1 selective blocker for one day medication.
2.Membrane
permeation
controlled
system:-In
this
system the drug reservoir is totally embedded in a compartment
molded between a drug-impermeable backing laminate and a rate
controlling polymeric simply by diffusion process through the
membrane The pores. In the reservoir compartments the drug solids
are dispersed homogenously in a solid polymeric matrix (e.g.
polyisobutylene) suspended in the unleachable viscous liquid medium
(e.g. silicon fluid) to form a gel-like suspension, or dissolved in a
releasable solvent (e.g. alkyl alcohol) to form a gel like in solution. The
rate controlling membrane, can be either a microporous or non-porous
polymeric membrane e.g. ethylenevinyl acetate copolymer, having
specific drug permeability. On the top surface of the polymeric
membrane a thin layer of drug compatible adhesive polymer, e.g.,
silicone adhesives, can be applied, to provide intimate contact of the
transdermal system with the skin surface. The release rate from this
transdermal system can be tailored by varying the polymer
composition, thickness of the rate controlling membrane , permeability
coefficient and adhesive. Examples of this system are TransdermScop
(Scopolamine- 3 days protection) of motion sickness and
TransdermNitro (Nitroglycerine-for once a day )medication of angina
pectoris.
20
3.Matrix diffusion controlled system:- In this approach, the

drug reservoirs are prepared by homogeneously dispersing drug
particles in a hydrophilic or lipophilic polymer matrix or combination of
both.. The resultant medicated polymer is then molded into a
medicated disc with a defined surface area and controlled thickness.
The dispersion of drug particles in polymer matrix can be accomplished
by either homogenously mixing the finely ground drug particles with a
liquid polymer or a highly viscous base polymer followed by cross
linking of the polymer chains or homogenously blending drug solids
with a rubbery polymer at an elevated temperature and/or under
vacuum. The polymer disc which contains drug reservoir is fixed onto
an occlusive base plate in a compartment fabricated from a drugimpermeable backing. The adhesive polymer is then spread to form a
strip of rim along the medicated disc. This matrix type of transdermal
system is best exampled by the nitroglycerinreleasing transdermal
therapeutic system. The advantage of matrix dispersion type
transdermal systemis the absence of the dose dumping since the
polymer cannot rupture.
4.Microreservoir type controlled system:- This system is

basically hybrid of reservoir and matrixdispersion type of drug delivery
system.In this approach, drug reservoir is formed by suspending the
drug in an aqueous solution of liquid polymer and then dispersing the
drug suspension homogeneously in a lipophilic polymer e.g.silicone
elastomers by high energy dispersion technique by shear mechanical
force to form thousands of unreachable, and microscopic spheres of
drug reservoirs. This technology has been utilized in the development
of Nitro disc. Release of a drug from a micro reservoir-type system can
follow either a partition-control or a matrix diffusion-control depending
upon the relative magnitude of solubility of the drug in the liquid
compartment and in the polymer matrix. cross linking of the polymer
chains or homogenously blending drug solids with a rubbery polymer
at an elevated temperature and/or under vacuum. The polymer disc
which contains drug reservoir is fixed onto an occlusive base plate in a
compartment fabricated from a drug-impermeable backing. The
adhesive polymer is then spread to form a strip of rim along the
medicated disc. This matrix type of transdermal system is best
exampled by the nitroglycerinreleasing transdermal therapeutic
system. The advantage of matrix dispersion type transdermal systemis
the absence of the dose dumping since the polymer cannot rupture.
Drug-impermeable backing laminate and a rate controlling polymeric
simply by diffusion process through the membrane The pores. In the
reservoir compartments the drug solids are dispersed homogenously in
21
a solid polymeric matrix (e.g. polyisobutylene) suspended in the

unleachable viscous liquid medium (e.g. silicon fluid) to form a gel-like
suspension, or dissolved in a releasable solvent (e.g. alkyl alcohol) to
form a gel like in solution. The rate controlling membrane, can be
either a microporous or non-porous polymeric membrane e.g.
ethylenevinyl acetate copolymer, having specific drug.
Prepration And Evaluation

Transdermal patches of clopidogrel bisulfate were prepared by solvent
casting technique Ethanolic solution of polymer and drug along with
polyethylene glycol (plasticizer) was prepared. The homogenous
mixture was poured into plastic mould. The solvent was allowed to
evaporate at controlled rate by placing an inverted funnel over the
plastic mould. The control of evaporation is necessary for uniform
drying of films. The drying was carried out at room temperature for
duration of 24 hours. After 24 hours the dry films was removed from
plastic mould and stored in desiccators until used.
Table 1: Formulation Composition of Blank Transdermal Patch
So.No
.
Formulatio
n Code
Plan
chitosan
(g)
Polymer
A (g)
Polymer
B (g)
Chitosa
n/
HPMC
(g)
F1
1.8%
2.3%
2.8%
F2
1.8%
2.3%
2.8%
F3
1.8%
2.3%
2.8%
1.1%
10
F4
2.1%
11
1.2%
22
Table 2: Composition of various Drug Loaded Transdermal Patch

So.no.
Formulati
on
Polymeri
c
Polymers
Plasticiz
er
ketoprof
en
code
w/w%
solution w/v%
(%)
(Glycerol
)
D1
2.3
Plain
chitosan
15
20
D2
2.3
25
20
D3
2.3
Polymer A 15
20
D4
2.3
Polymer A 25
20
D5
2.3
Polymer B 15
20
D6
2.3
Polymer B 25
20
D7
2.3
Plain
15
chitosan+
20
D8
HPMC
(75:25)
20
Plain
chitosan
25
Plain
chitosan+
HPMC
(75:25)
Drug-loaded matrix-type transdermal patches of Repaglinide were
prepared by using solvent casting method. A petri dish with a total
23
area of 44.15cm2 was used. Polymers were accurately weighed and

dissolved in 10mL of water,methanol (1:1) solution and kept
aside to form clear solution. Drug was dissolved in the above solution
and mixed until clear solution was obtained. Polyethylene glycol 400
(30%w/w of total polymer) was used as plasticizer and propylene
glycol (15%w/w of total polymer) was used as permeation enhancer.
The resulted uniform solution was cast on the petri dish, which was
lubricated with glycerin and dried at room temperature for 24h. An
inverted funnel was placed over the petri dish to prevent fast
evaporation of the solvent. After 24h, the dried patches were taken
out and stored in a desiccator for further studies.
1.Folding Endurance:- A strip of specific area (2cm*2cm) was

cut evenly and repeatedly folded at the same place till it broke. The
number of times the film was folded at the same place without
breaking gave the value of the folding endurance.
2.Tensile Strength:- The tensile strength of the patch was

evaluated by using the tensiometer (Erection and instrumentation,
Ahmedabad). It consists of two load cell grips. The lower one was fixed
and upper one was movable. Film strips with dimensions of 2*2cm
were fixed between these cell grips, and force was gradually applied till
the film broke. The tensile strength was taken directly from the dial
reading in kg.Tensile strength= F/a.b (1+L/l)F is the force required
to break; a is width of film; b is thickness of film; L is length of film; l is
elongation of film at break point
3.Thickness:- Patch thickness was measured using digital

micrometer screw gauge at three different places, and the mean value
was calculated.
4.Content uniformity test:- Select 10 patches but content is

determined for individual patches. If 9 out of 10 showed content
between 85-115% of the specified value and no one has shown 75125% of the specified value,it means the test has been passed but if 3
patches shown the content between 75-125% then taken 20 additional
patches and further test performed. If these 20 patches shown content
between 85-115 % ,then the patches passed the test.
5.Uniformity of dosage unit test:A patch of accurately weigh is cutted in to small pieces and transferred
to volumetric flash containing specific volume of suitable solvent for
dissolution of drug and then sonicated for a limited period of time for
complete extraction of drug from pieces and then mark the volume
24
with the same solvent. The solution obtained kept untouched for 1
hour to settle down then supernatant diluted as required. The dilute
solution was filtered by membrane having pore size 0.2m and
analyzed with suitable analytical ( HPLC / UV) technique and the
calculation was done for drug content.
6.Percentage Moisture Content:- The prepared films were
weighed individually and kept in a desiccator containing fused calcium
chloride at room temperature for 24h. After 24hours.
In Vivo Drug Release Studies :In Vitro drug release studies were performed by using a Franz
diffusion cell with a receptor compartment capacity of 60mL.
The cellulose acetate membrane was used for the determination
of drug from the prepared transdermal matrix-type patches. The
cellulose acetate membrane having a pore size 0.45 was
mounted between the donor and receptor compartment of the
diffusion cell. The prepared transdermal film was placed on the
cellulose acetate membrane and covered with aluminum foil. The
receptor compartment of the diffusion cell was filled with
phosphate buffer pH 7.4. The whole assembly was fixed on a hot
plate magnetic stirrer, and the solution in the receptor
compartment was constantly and continuously stirred using
magnetic beads, and the temperature was maintained at 32
0.5C, because the normal skin temperature of human is 32C.
The samples were withdrawn at different time intervals and
analyzed for drug content spectrophotometrically. The receptor
phase was replenished with an equal volume of phosphate buffer
at each sample withdrawal.
In Vitro Permeation Studies:An in vitro permeation study was carried out by using Franz
diffusion cell. Full thickness abdominal skin of male Wistar rat
weighing 200 to 250g was used. Hair from the abdominal
region was removed carefully by using an electric clipper; the
dermal side of the skin was thoroughly cleaned with distilled
water to remove any adhering tissues or blood vessels,
equilibrate for an hour in phosphate buffer pH 7.4 before starting
the experiment, and was placed on a magnetic stirrer with a
small magnetic needle for uniform distribution of the diffusant.
The temperature of the cell was maintained at 320.5C
using a thermostatically controlled heater. The isolated rat skin
piece was mounted between the compartments of the diffusion
cell, with the epidermis facing upward into the donor
compartment. Sample volume of 5mL was removed from the
receptor compartment at regular intervals, and an equal volume
25
of fresh medium was replaced. Samples were filtered through

watman filter and were analyzed using Shimadzu UV 1800
double-beam spectrophotometer (Shimadzu, Kyoto, Japan). Flux
was determined directly as the slope of the curve between the
steady-state values of the amount of drug permeated (mg*cm2)
versus time in hours and permeability coefficient was deduced
by dividing load (mg*cm2).
Result and Discussion

Preliminary Study:All the batches of transdermal patch showed thickness variation range
from0.12 to 0.20mm as shown in . High thickness of batch P4 anP5
was found, it may be due to low solubility of ethyl cellulose in solvent
render uneven distribution of polymer layer. All the batches of
transdermal patch showed tensile strength and % elongation in
uniform range from 16 to 22 and 17.5 to 22.5, respectively, except
batches P4 and P5 may be due to poor solubility of ethyl cellulose and
weak bond formation . Hence batches P4 and P5 were eliminated for
further study. Batch P1 containing PVA:PVP shows fast release of drug
(101.26% at 8h) from patch due to burst effect of PVP and also more
solubility in water. So batch P1 was also eliminated.The free amino
group of chitosan was reacted with aldehyde in presence of acid to
form Schiffs base. Aldehydes were selected based on their film
forming capacity with the polymer. The percent aldehyde conversion
and carbon chain length of the aldehyde, affected the film
characteristics. The FTIR spectrum of plain chitosan, polymer A and
polymer B was taken to confirm themodification of chitosan and
stability of drug. Chitosan showed peak at 1637cm-1 corresponding to
amino groups. In contrast,after formation of imino group (-C=N-) a new
peak appeared at 1541cm1for polymer A and at 1558 cm-1 for
polymer B (fig. 1). FTIR of pure etoricoxib and drug loaded membranes
26
were also obtained to find out if there was any chemical interaction
between drug and the polymer. Etoricoxib showed characteristic peak
at 1143 cm-1 corresponding to sulphone groups (-S=O) and did not
alter even after loading into the membrane, this confirms stability (no
interaction) of the drug (fig. 2). FTIR of HPMC and chitosan/HPMC
blend were obtained to find out if there was any interaction between
HPMC and chitosan. FTIR of drug loaded chitosan/HPMC blend film was
also obtained to evaluate the chemical interaction between drug and
chitosan/HPMC blend. Etoricoxit characteristic peak at 1143 cm-1
remained unchanged which confirmed the stability of drug. FTIR
Spectrum of blank polymeric films: A: chitosan, B: chitosan modified
with acetaldehyde and C: chitosan modified with propionaldehyde with
acetaldehyde and C: chitosan modified with propionaldehyde.
All the drug loaded films were found to be quite uniform in thickness.
The percent flatness of drug loaded films was ideal All films showed an
increase in moisture uptake with an increase in relative humidity. The
increase in moisture uptake may be attributed to the hygroscopic
nature of polymer-glycerol composite film. All the films showed
increase in weight with time . The films with modified polymer showed
low swelling index as compared to that of films with plain chitosan .
Different formulation showed different water vapour transmission rate.
The bursting strength has linear correlation with increase in
27
concentration of plasticizer It was noticed that formulation D8 showed

highest tensile strength of 4.728 kg/cm2 (Chitosan/HPMC blend with
30% glycerol) where as formulation D2 showed 4.258 Kg/cm 2.
Formulation D3 (modified with acetaldehyde with 30% glycerol)
showed low tensile strength of 2.690 kg/cm2. Formulation D2, D4 and
D8 showed highest percent elongation of 80% where as formulation D5
shows low percent elongation of 40%.
The selected formulations loaded with etoricoxib were subjected to
invitro drug release. Invitro diffusion studies across dialysis membrane
and rat skin was conducted using diffusion cell fabricated with the help
of funnel and beaker assembly. Drug release from swellable and
erodible hydrophilic matrix can be attributed to polymer dissolution
(matrix erosion mechanism), drug diffusion through the gel layer or
combination of both. When the data was plotted as cumulative
percentage of drug permeated versus time and the data for
cumulative percentage drug release were depicted in The data were
subjected to first order equation and the regression value was found to
be in the range of (R2 = 0.8825 0.9987) which confirm first order
release pattern. Further to find out whether diffusion is involved in the
drug release, the data was subjected to Higuchis equation.
The lines obtained were comparatively linear (R2 = 0.84860.9765)
suggesting the diffusion may be mechanism of drug release. To confirm
further the release mechanism of drug, the data was subjected to
Korsmeyers-Peppas equation. The release exponent n value was
determined, based on n value it can be explained that incorporated
drug release by the anomalous (Non-Fickian) type of diffusion,
involving swelling of the polymer matrix, as is evident by the slope
values of more than 0.5 but less than 1 for the plot of log cumulative
amount release Vs log time (Korsmeyers-Peppas plot). Except in case
of formulation C5 which showed Non-Fickian super case II (slope =
1.180). When the average rate constant of the formulation were
studied, it was observed that formulation C8 showed comparatively
lower rates of release of drug, the results are shown in Among all the
prepared films, C8 (chitosan/HPMC blend in the ratio of 75:25; crosslinked with sodium citrate) would be a better formulation based on the
in vitro permeation studies as it released the drug in sustained release
pattern for 24 hours without significantly releasing the drug in a burst
manner in the initial hours. Among the non cross-linked formulation D3
would be a better formulation based on the in vitro permeation studies
and first order rate constant.
drug release kinetics parameters of release studies through dialysis
membrane
28
The skin permeation studies were carried out using rat skin. The
apparatus for the study was arranged in the same manner as for
dialysis membrane permeation study. The results are shown in the . As
done in previous experiment, the drug permeation data was plotted
( according to first order, Higuchis and Korsemeyer-Peppa equation to
know the release mechanisms. The formulations showed the fair
linearity with respect to first order .
(R2 = 0.98430.9138) and Higuchis equations (R2 = 0.96960.9356)
hence to confirm precisely the domination mechanism; the data was
plotted according to Korsemeyers equation. The lines obtained were
linear (R2 = 0.94610.9655), slope values vary between (0.6160 and
0.6792).
were eliminated for further study. Batch P1 containing PVA:PVP
shows fast release of drug (101.26% at 8h) from patch due to burst
effect of PVP and also more solubility in water. So batch P1 was also
eliminated.The free amino group of chitosan was reacted with
aldehyde in presence of acid to form Schiffs base. Aldehydes were
selected based on their film forming reagent.
In Vitro cumulative drug release studies of formulation cross linked

sodium citrate
29
In Vitro cumulative drug release studies of formulation cross linked

sodium citrate
30
CONCLUSION
This article provide an valuable information regarding the transdermal
drug delivery systems and its evaluation process details as a ready
reference for the research scientist who are involved in TDDS. The
foregoing shows that TDDS have great potentials, being able to use for
both hydrophobic and hydrophilic active substance into promising
deliverable drugs. To optimize this drug
delivery system, greater understanding of the different mechanisms of
biological interactions, and polymer are required. TDDS a realistic
practical application as the system. Since 1981, transdermal drug
delivery systems
have been used as safe and effective drug delivery devices.
Their potential role in controlled release is being globally exploited
by the scientists with high rate of attainment. If a drug has right mix of
physical chemistry and pharmacology, transdermal delivery is a
remarkable effective route of administration. Due to large advantages
of the TDDS, many new researches are going on in the present
31
day to incorporate newer drugs via the system. A transdermal patch

has several basic components like drug reservoirs, liners,
adherents, permeation enhancers, backing laminates, plasticizers and
solvents, which play a vital role in the release of drug via skin.
After preparation of transdermal patches, they are evaluated for
physicochemical studies, in vitro permeation studies, skin irritation
studies,
animal studies, human studies and stability studies. But all prepared
and evaluated transdermal patches must receive approval
from FDA before sale. Future developments of TDDSs will likely focus
on the increased control of therapeutic regimens and the
continuing expansion of drugs available for
use. Transdermal dosage forms may provide clinicians an opportunity
to offer more therapeutic options to their patients to optimize their
care.
References
Jain, NK. Controlled and Novel Drug Delivery, CBS Publishers, and
Distributors, 2002; 107.
Chien, YW. Novel drug delivery systems, Drugs and the
Pharmaceutical Sciences, Vol.50, Marcel Dekker, New York, NY; 1992;
797.
Wilkosz MF. Transdermal Drug Delivery: Part I. U.S. Pharmacist. Jobson
publication; 28:04; 2003
Bharadwaj S, Gupta GD, Sharma VK. Topical Gel: A Novel Approach for
drug delivery. J Chem. Bio. Phy. Sci. 2012; 2(2): 856-867
.
32
Sharma N, Parashar B, Sharma S, Mahajan U. Blooming Pharma

Industry with Transdermal Drug Delivery System. Indo Global J Pharm.
Sci. 2012; 2(3): 262-278.
arwhekar G, Jain DK, Paditar VK. Formulation and Evaluation of
Transdermal drug delivery system of Clopidogrel Bisulfate. Asi. J.
Pharmacy Life Sci. 2011; 1(3): 269-278
Willams AC, Barry BW. Penetration Enhancers. Adv. Drug Del. Rev
2004; 56: 603-618.
Pellet M, Raghavan SL, Hadgraft J, Davis AF. The application of
supersaturated systems to percutaneous drug delivery, In: Guy R.H
and Dekker, Inc., New york 2003, pp. 305-326.\
Brown MB, Jones SA. Hyaluronic acid: a unique topical vehicle for
localized drug delivery of drugs to the skin. JEDV 2000; 19: 308-318.
Tsai JC, Guy RH, Thornfeldt CR, Gao WN, Feingold KR, Elias PM.
Metabolic Approaches to Enchance Transdermal drug delivery. J. Pharm.
Sci. 1998; 85: 643-648.
Willams AC, Barry BW. Penetration Enhancers. Adv. Drug Del. Rev 2004;
56: 603-618.
Pellet M, Raghavan SL, Hadgraft J, Davis AF. The application of
supersaturated systems to percutaneous drug delivery, In: Guy R.H
and Dekker, Inc., New york 2003, pp. 305-326
Brown MB, Jones SA. Hyaluronic acid: a unique topical vehicle for
localized drug delivery of drugs to the skin. JEDV 2000; 19: 308-318.
Tsai JC, Guy RH, Thornfeldt CR, Gao WN, Feingold KR, Elias PM.
Metabolic Approaches to Enchance Transdermal drug delivery. J. Pharm.
Sci. 1998; 85: 643-648.
Berner B, John VA. Pharmacokinetic characterization of Transdermal
delivery system.
J. Clin. pharmaco. 1994; 26(2): 121-134
Aggarwal G. Development, Fabrication and Evaluation of Transdermal
Drug Delivery A Review. Pharmainfo.net. 2009
33
Kumar JA, Pullakandam N, Prabu SL, Gopal V. Transdermal drug delivery

system: an overview. Int. J. Pharm. Sci. Rev. and Res. 2010; 3(2): 49
. Barhate SD, Bavaskar KR, Saoji YS, Potdar M, Gholap TN.
Development of Transdermal drug
delivery system of Ketoprofen. Int. J. Parma. Res. Develop. 2009; 1(10):
1-7 Keleb E, Sharma RK, Mosa EB, Aljahwi AZ.
Transdermal Drug Delivery System- Design and Evaluation. Int. J. Adv.
Pharm. Sci. 2010; 1:201-211
Prausnitz, M.R., Langer,R., 2008. Transdermal drug delivery,Nat
Biotechnol.26(11),1261-1268
Kaestli,L.Z., Wasilewski-Rasca,A.F., Bonnabry, P., Vogt-Ferrier N.,2008.
Use of transdermal drug formulations in the elderly. Drugs Aging.
25(4), 269-280.
Vishwakarma,S.K.,NiranjanS.K.,Irchhaiya,R.,Kumar,N .,Akhtar,A.,2012.A
Novel transdermal drug delivery system,International Journal of
research of pharmacy 3(8),39-44
Shingade,G.M.,Aamer,Q.,Sabale,P.M.,Gramprohit
N.D.,Gadhave,M.V.,Jadhv,S..L,Gaikwad, D.D.2012.,Review on: recent
trend on transdermal drug delivery system, Journal of Drug Delivery &
Therapeutics 2 (1) , 66-75
Hanumanaik, m., Patil,u., Kumar,g., Patel,s.k. Singh,i.,
Jadatkar,k.,2012. design, evaluation and recent trends in transdermal
drug delivery system: a review, International Journal of pharmaceutical
sciences and research 3(8),2393-2409
Rastogi, V., Yadav,P., 2012. Transdermal drug delivery system: An
overview, Asian Journal Of Pharmaceutics 6(3),161-170
Arunachalam,A., ,Karthikeyan, M., Kumar,V. D., Prathap, M.,
Sethuraman, S., Ashutoshkumar, S., Manidipa, S., 2010.Transdermal
Drug Delivery System: A Review, Current Pharma Research 1(1) , 7081.
Kapoor D., Patel, M. and Singhal M., 2011.Innovations in Transdermal
drug delivery system, International PharmaceuticaSciencia 1 (1) , 5461
Rajesh, N., Siddaramaiah, Gowda, D.V.,Somashekar. C.N., Formulation
and evaluation of based on transdermal drug delivery, Pharmacy
Pharm. Sci., 2010; 2, 142-147
34
Vijayan, V., Sumanth, M.H., Suman, L., vinay, T.,

Srinivasrao, D., Kumar. K.J., Development and physiochemical, in-vitro
evaluation of transdermal Patches. J. Pharm.sci. & Res., 2010; 2(3),
171-177.
Shivaraj, A. Selvam, R.P., Mani, T.T., Sivakumar,T., Design and
evaluation of transdermal drug delivery Int. J. Pharm. Biomed. Res.
2010; 1(2), 42-47.
Bharkatiya, M., Nema, R.K., Design and characterization of drug free
patches fortransdermal application, Int. J. Pharm, Sci., 2010;2 (1), 3539.
Ramkanth. S., Alagusundaram M., Gnanaprakash K., Rao K.M.,
Mohammed S.T.S., Paneer, K., Chetty M.C., Design and characterization
of matrix type transdermal drug delivery System
Int. J. Pharm Res. 2010; 1 (1) 1-5.
Sanjoy, m., Thimmasetty, j., Ratan, G.N.,Kilarimath, B.H., Formulation
and evaluation of
transdermal patches. Int. Res. J. Pharm.2011; 2 (1), 237-248. Patel,
J.H., Patel, J.S., Desai B.G., Patel, K.D.,Design and Evaluation of
Amlodipin besilate
35
36
37
38

Transdermal Drug Delivery System1

Transféré par

Informations du document

Description originale:

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Transdermal Drug Delivery System1

Transféré par

Droits d'auteur :

Formats disponibles

TRANSDERMAL DRUG DELIVERY SYSTEM

Transdermal patch of scopolamine is the first transdermal patch which

release drugs in a controlled way into the human body, transdermal

SRMSCET (PHARMACY) BAREILLY

3.Adhesive:- Serves to adhere the patch to the skin for systemic

delivery of drug. Ex: Acrylates, Polyisobutylene, Silicones.

TYPES OF TRANSDERMAL PATCHES

e) Matrix system:i. Drug-in-adhesive system:- In this type the drug reservoir is

SRMSCET (PHARMACY) BAREILLY

ii. Matrix-dispersion system: In this type the drug is dispersed

f) Microreservoir system: In this type the drug delivery system is

VARIOUS METHODS FOR PREPARATION TDDS:a.

Asymmetric TPX membrane method:- A prototype patch

b. Circular teflon mould method:- Solutions containing

C. Mercury substrate method:- In this method drug is

homogenous dispersion and poured in to a leveled mercury

d.By using IPM membranes method:- In this method drug

e.By using EVAC membranes method:- In order to

f.Aluminium backed adhesive film method:- Transdermal

g.Preparation of TDDS by using Proliposomes:- The

drying, the temperature of the water bath is adjusted to 20-30C. Drug

h.By using free film method:- Free film of cellulose acetate is

IDEAL PROPERTIES OF TDDS

Optimum partition coefficient required for the therapeutic action of

SRMSCET (PHARMACY) BAREILLY

Advantages of Transdermal drug delivery system:Avoidance of first pass metabolism of drugs.

FACTORS AFFECTING TRANSDERMAL DRUG DELIVERY

Regional skin site

Layers of skin:- Three major layers of the skin are

SKIN :-Structure of Skin The human skin is a mutilayered organ

Epidermis:-The epidermis is a stratified, squamous, keratinizing

Dermis:-The dermis is the inner and larger (90%) skin layer,

Hypodermis:- The hypodermis is the adipose tissue layer which is

SRMSCET (PHARMACY) BAREILLY

Aim and Project

SRMSCET (PHARMACY) BAREILLY

Pfister WR,.et al.,(1990):- Part I of this article reviews the

Jonathan Hadgraft,.et al.,(1999):- The skin has an extremely

Jain Amit.k,.et al,.(2008):- Third-generation delivery systems

microneedles, thermal ablation, microdermabrasion, electroporation

Robert Langer,.et al.,(2003):- Transdermal delivery represents

Heather A.E. Benson:- 1987There is considerable interest in the

P.M.Patil,.et al,.(2012):- Drug delivery system relates to the

Nikhil Sharma,.et al.,(2011):- There has been little change in the

SRMSCET (PHARMACY) BAREILLY

explores the overall study on transdermal drug delivery system (TDDS)

Kumar, J. Ashok,.et al.,(2004):- Today about 74% of drugs are

Anubhav Arora,.et al.,(2014):- Skin makes an excellent site for

SRMSCET (PHARMACY) BAREILLY

Ptel J Houk,.et al.,(1999):- The mechanism of action of

K.Alvin,.et al.,(2006):- This review describes enhancement

SRMSCET (PHARMACY) BAREILLY

SRMSCET (PHARMACY) BAREILLY

Fig.7. Different route of skin penetration

SRMSCET (PHARMACY) BAREILLY

Considerations for polymer selection in transdermal

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

Polymers used in transdermal system in versatile

SRMSCET (PHARMACY) BAREILLY

Release liners:- The patch is covered by protective liner during

Drug:-Transdermal delivery of drugs has taken a surge ofpopularity

Other excipients:Plasticizers:-Palsticizers have also been used in many formulations

Solvents:-Various solvents such as methanol, chloroform, acetone,