Transdermal drug delivery systems (TDDS), also known as patches, are dosage forms designed to deliver drugs across a patient's skin for systemic effects. TDDS provide advantages over oral and injectable routes by increasing compliance, avoiding first-pass metabolism, and allowing continuous drug delivery. For successful transdermal delivery, drugs must have certain physicochemical properties that allow penetration through the skin layers. TDDS consist of a drug reservoir containing the drug within an adhesive matrix or dispersed in an adhesive polymer. Rate-controlling membranes or adhesives are used to control drug release. Absorption occurs primarily through the stratum corneum via intracellular or intercellular routes or through hair follicles and sweat glands.

1. TRANSDERMAL DRUG
DELIVERY SYSTEM
Presented by
Dasara Thanmayi

2. ABSTRACT
Transdermal drug delivery systems (TDDS), also known as
“patches,” are dosage forms designed to deliver a therapeutically
effective amount of drug across a patient’s 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. 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. The TDDS review articles provide
valuable information regarding the transdermal drug delivery
systems and its evaluation process details as a ready reference for
the research scientist who is involved in TDDS.

3. INTRODUCTION
Transdermal therapeutic systems are defined self
contained ,self discrete dosage form ,which when
controlled rate to the systemic circulation.
Transdermal patch uses a special membrane to control
the release rate at which the liquid drug contained
patch reservoir can pass into skin and into blood
stream.
Transdermal delivery also allows continous input drugs
with short biological half lives and eliminates pulsed
delivery into systemic circulation which is responsible
for undesirable side effects

4. ADVANTAGES
It delivers a steady infusion of drug over an
extended period of time.
It increases the therapeutic value of many drugs by
avoiding specific problems associated with the
drug.
Self medication is possible with this type of
system.
The drug input can be terminated at any point of
time by removing the patch.
It is mostly useful in patients who are nauseated or
unconciousness.

5. DISADVANTAGES
The drug must have desired physiochemical
properties for penetration through stratum
corneum.
Heat, cold and sweating prevent the patch from
sticking to the surface of the skin.
The adhesive used may not adhere well to all types
of skin.
This system is may not be economical for some
patients.

6. APPLICATIONS
Transdermal patch of nicotine which releases
nicotine in controlled dose to help with cessation
of tobacco smoking.
Nitroglycerine patches are also sometimes
prescribed for the treatment of angina
Transdermal form of the MAO selegline ,become
the first transdermal delivery agent for anti
depressant
Transdermal delivery agent for the attention deficit
hyperactivity disorder [ADHD].

7. ANATOMY OF SKIN
 Skin is an extensive organ of body covering an
area of about 2m2. with thickness of 1mm.
 The skin separates the underlying blood
circulation from outside environment.
Human skin consists of three layers:
• The stratified, vascular,cellular
epidermis
• Underlying dermis and
• hypodermis

9. EPIDERMIS:
 It is divided into stratum corneum and stratum
germinativum.
 Stratum corneum is outermost layer and consists
of many layers of flattened, keratinized cells
responsible for barrier function of skin and
behaves as a primary barrier to percutaneous
absorption.
stratum granulosum
Stratum corneum stratum lucidum
stratum spinosum

10. DERMIS:
 It is made up of network of collagen fibers and
this network or gel structure is responsible for
the elastic properties of the skin.
 Upper portion of dermis is formed into ridges
containing lymphatics and nerve endings.
SUBCUTANEOUS:
 This is a sheet of fat containing tissue known as
superficial fascia.

11. MARKETED PRODUCTS OF
TRANS DERMAL DRUG
DELIVERY SYSTEM
S.NO PRODUCT ACTIVE
DRUG
TYPE OF
PATCH
PURPOSE
1 nitrodur nirtoglycerine matrix angina pectoris
2 deponit nirtoglycerine drug in
adhesive
angina pectoris
3 lidoderm lidocaine drug in
adhesive
anaesthetic
4 Duragesic Fentanyl Reservoir Pain relief patch
5 Transdermsco
p
Scopolamine Matrix Motion sickness

12. BASIC COMPONENTS OF
TRANSDERMAL DRUG DELIVERY
Polymer matrix (rate controlling polymer)
The drug
Permeation enhancers
Adhesive
Backing layer

13. POLYMER MATRIX:
 Rate controlling polymer is in the form of
membrane or matrix
 It is responsible for control of release by
diffusion of drug through the rate controlling
membrane.
Polymers used:
 Natural polymers:cellulose derivatives, zein ,
gelatin ,shellac,waxes,gums and natural rubber.
 Synthetic elastomer: polysiloxane,silicon
rubber,nitrile,acrylonitrile,butyl rubber.

14. DRUG:
for successful developing of transdermal
delivery drug should be chosen with great care .
 physicochemical properties :
–molecular weight less than 1000 daltons.
–Affinity for both lipophilic &hydrophilic
phases.
–Drug should have low melting point.
 Biological properties:
−Half life of drug should be short.
−It should be potent with daily dose of few
mg/day.
−Non irritant to skin.

15. IDEAL PROPERTIES OF DRUG
USED IN TDDS
PARAMETERS PROPERTIES
• Dose Should be low
• Half life 10 or less
• Partition coefficient <400
Log P (octonal -
water) between1-4
• Skin permeability
coefficient
>0.5X10-3 cm/hr
• Skin reaction Non irritating and non
sensitizing
• Oral bioavailability Low
• Therapeutic index Low

16. Permeation/penetration/sorption enhancers:
these are the agents that interact with skin
constituents to promote the drug flux/absorption.
the flux J,of drugs across the skin can be
written as
J=D dc/dx
where D=diffusion coefficient
C=concentration of diffusing species
X=spatial coordinate.
 Solvents: methanol,ethanol,omso,dmf,glycerol.
 Surfactants:anionic dioctyl sulfosuccinate,sls.
cationic puronic CF 127,pluronic F-68
 Binary systems: propylene glycol.

17. ADHESIVES:
 it is an important component which is necssary
for attachment of TDDS.
 the fastening of all transdermal devices to the
skin has been done by using a pressure sensitive
adhesive
 Adhesive systems should fulfil the following
criteria
−Should adhere to the skin aggresively & easily
removed
−Should not leave an unwashable residue.
−Should not irritate or sensitize the skin.
−Should have intimate contact with the skin.
−Permeation of the drug should not be affected.
−Should not effect the normal functioning of the
skin.

18. BACKING MEMBRANE:
It is an impermeable membrane that protects
the product during the use on the skin.
Prevents the drug from leaving the dosage
form through top and protects the formulation
throughout shelf life and during wear period.
Must be compatible with the formulation.
eg:metallic plastic laminate ,plastic
backing with absorbent pad and occlusive base
plate (aluminium foil),adhesive foam pad
(flexible polyurethane) with occulsive base
plate (aluminium foil disc) etc.

19. ROUTES OF DRUG ABSORPTION
THROUGH SKIN
The drug absorption through skin occurs by
–Transepidermal absorption
–Transfollicular (shunt pathway absorption)
–Clearance by local circulation.
Transepidermal absorption:
–Stratum corneum is the main resistance for absorption
–Permeation involves partitioning of the drug into the
stratum corneum
–Hydrophilic drug pass through cell of stratum
corneum(intracellular).
–Non-polar drugs diffuse through non-aqueous lipid
matrix between the protein filaments.

21. Transfollicular absorption:
−The skin’s sebaceos and eccrine (sweat)glands
are considered as shunts for by passing the
stratum corneum.
−Follicular route is important for permeation
because the opening of follicular pore is large
and sebum aids in diffusion of the penetrant.
−After partitioning into sebum,the drug diffuses
the depths of epidermis.
Clear by local circulation:
−the drugs enter into the systemic circulation
from papillary plexus in upper epidermis.

23. GENERAL METHOD OF
PREPERATION FOR TDDS
DRUG PREPARATION
DRUG/ADHESIVE SOLUTION
PREPERATION
RELEASE LINER DRUG/ADHESIVE COATINGS
BACKING
FILM LAMINATION
DIE CUTTINGS
SYSTEM PACKAGING
FINAL PRODUCT

24. FORMULATION APPROACHES
USED IN THE DEVELOPMENT OF
TDDS
Membrane permeation - controlled system
Adhesive dispersion - type systems
Matrix diffusion – contolled systems
Micro reservoir type or microsealed dissolution –
controlled systems.

25. MEMBRANE PERMEATION –
CONTROLLED SYSTEM
The drug reservoir is totally encapsulated in a
shallow compartment moulded from a drug-
impermeable metallic plastic laminate and a rate
controlling polymeric membrane which may be
microporous or non porous(ethylene vinyl acetate)
Eg:nitroglycerine-releasing transdermal
system(transdermal-nitro)for once a day in angina
pectoris

26. The intrinsic rate of drug release from this type is ,
where,
Cr = drug concentration in the reservoir compartment
pa & pm = permeability coefficient of adhesive and the rate
controlling membrane respectively.
for microporous membrane , pm is the sum of permeability
coefficients for simultaneous penetration across the pores and
polymeric material , hence
dm ha

27. Preparation: these products consists of three substrates
held together by two layers of drug containing adhesive
Drug is processed into physical or chemical form
Drug adhesive components &excipients are mixed
Solvent is added to above mixture to form uniform
solution
These adhesive components are deposited as thin film on
moving substance and dried
The lamination of adhesive film and other layers is done
The lamination then printed &die cut into final dosage
form
Packing is done in foil pouches

28. ADHESIVE DISPERSION-TYPE
SYSTEM
This system is simplified form of the membrane
permeation controled system
Prepration the drug reservoir is formulated by
directly dispersing the drug in an adhesive polymer
eg;poly(isobutylene)or (acrylate)adhesive and then
spreading the medicated adhesive,by solvent
casting or hot melt ,onto a flatsheet of drug
impermeable metallic plastic backing to form a
thin drug reservoir layer

29. On the top of the drug reservoir layer,thin layers of
non-medicated,rate controlling adhesive polymer of a
specific permeability and constant thickness are
applied to produce an adhesive diffusion-controlled
delivery system
Eg:isosorbide dinitrate-releasing transdermal
therapeutic system(frandol tape)for once aday in
angina pectoris
The rate of drug release in this system is defined by
ha
CR
where , = partition coefficient for the
interfacial partitioning of the drug from the reservoir
layer to adhesive layer

30. MATRIX DIFFUSION-
CONTROLLED SYSTEM
The drug reservoir can be formed by dissolving drug
and polymer in a common solvent folowed by solvent
evaporation in a mould at an elevated temperature and
vaccum
The advantage of this type of system is the absence of
dose dumping since polymer cannot rupture
Eg:nitroglycerine-releasing transdermal therapeutic
system at a daily dose of 0.5gm/cm2 for therapy of
angina pectoris
The rate of drug release from this type is given by
1/2

31. Preparation the drug reservoir is prepared by
homogenously dispersing drug particles in a
hydrophilic or lipophilic polymer matrix
Moulded into a medicated disc with a defined surface
area and controlled thickness
The dispersion of drug particles in the polymer matrix
can be accomplished by mixing the drug particles with
Liquid polymer highly viscous base polymer
followed by crosslinking of the
polymer chains
or
Blending drug solids with a rubbery
polymer
At an elevated temperature

32. MATRIX DIFFUSION-CONTROLLED SYSTEM

33. MICRORESERVOIR TYPE OR
MICROSEALED DISSOLUTION-
CONTROLLED SYSTEM
This is the combination of reservoir and matrix
diffusion type drug delivery systems
Drug reservoir is formed by first suspending the drug
solids in an aqueous solution of a water soluble liquid
polymer and then dispersing the drug suspension
homogenousy in a lipophilic polymer such as silicon
elastomers by high dispersion technique
Eg:nitroglycerine-releasing transdermal
system(nitrodisc)for once a day therapy of angina
pectoris

34. EVALUATION OF TRANSDERMAL
DRUG DELIVERY SYSTEM
Physico-chemical evaluation
In –vitro evaluation
In –vivo evaluation

35. PHYSICO-CHEMICAL
Drug -polymer interaction studies:
interaction studies were conducted on the
medicated TDDS formulations by comparing them
with the pure drug and placebo formulations on the
basis of thermal analysis (DSC), fouriter transform
infrared spectroscopy (FTIR) ,ultra violet (UV)and
chromatographic techniques by comparing their
physicochemical properties like assay , melting
point ,wave number and absorption maxima , RF
value etc.

36. Physical appearance: Patches were visually
inspected for colour , clarity ,flexibility and
smoothness
Thickness uniformity : transdermal film is
determined by travelling microscope ,dial gauge
,screw gauge or micrometer at different points of
the film.
Unifromity of weight: A specified area 1cm2 of
patch is to be cut in different parts of the patch and
is to be dried at 600c for 4 hours before testing and
weight variation is studied by individually
weighing 10 randomly selected patches and
calculating the average weight

37. Drug content determination: Accurately
weighed portion of film (about 100mg) is dissolved
in 100ml of suitable solvent and shaken
continously for 24 hrs
After sonication & subsequent filteration,drug
in solution is estimated against the reference
solution consisting of placebo films with the
suitable method(UV or HPLC technique)
Surface pH : transdermal films were allowed to
swell for 2 hours at 370c on the surface of an agar
plate, prepared by dissolving 2% (W/V)agar in
warm isotonic phosphate buffer of pH 5.5 then the
surface pH was measured by using pH paper placed
on the surface of the swollen patch .after 90 sec the
colour developed

38. Folding Endurance: it involves determining the
folding capacity of the films subjected to frequent
extreme conditions of folding.
It is determined by repeatedly folding the film at
the same place until it break.’
The number of times the films could be folded at
the same place without breaking is folding
endurance value.
Tensile strength: polymeric film was determined
with universal strength testing machine. The
sensitivity of the machine was 1gm

39. EVALUATION OF ADHESIVE
Shear adhesion test: shear adhesion strength is
determined by measuring (cohesive strength of an
adhesive polymer ) the time it takes to pull the tape
off the plate

40. Peel adhesive test : In this test, the force required
to remove an adhesive coating form a test substrate
is referred to as peel adhesion.

41. Tack properties:
Rolling ball tack test :- In this test, stainless
steel ball of 7/16” in diameter is released on an
inclined track so that it rolls down and comes
into contact with horizantal , upward facing
adhesive film.

42. Quick stick ( peel-tack) test: the peel force
required breaking the bond between an adhesive
and substrate is measured by pulling the tape away
from the substrate at 900 at the speed of 12
inch/min.

43.  Probe tack test: the tip of a clean probe is
contact with adhesive and bond is formed
between probe and adhesive.
the force required to pull the probe away from
the adhesive at fixed rate is recorded as tack and
it is expressed in grams.

44. IN–VITRO EVALUATION
Paddle over disc : this method the transdermal
system is attached to a disc or cell resting at the
bottom of the vessel which contain medium at
32±50c.

45. Cylinder modified usp basket :
this method is similar to the usp
basket type dissolution apparatus
,except that the system is attached to
the surface of a hollow cylinder
immersed in medium at 32 ±50c.
Reciprocatingdisc:-(uspapparatus
7) in this method patches attached to
holders are oscillated in small
volumes of medium. Allowing the
apparatus to be useful for systems
delivering low concentration of drug
. In addition paddle over extraction
cell method may be used.

46. In-vitro skin permeation
studies :the transdermal
system is applied to the
hydrophilic side of the
membrane(donor
compartment) and then
mounted in the diffusion
cell with lipophilic side in
contact with receptor fluid
(receptor compartment
usually temperature 32±50c
for membrane) . In verical
diffusion cell such as Franz
diffusion cell or Keshary-
chain (K-C)diffusion cell
and is continously stirred at
a constant rate.

47. IN-VIVO EVALUATION
animal model: In-vivo animals models are
preferred , because considerable time and
resources are required to carry out studies in
humans. Some of the species are used:-
mouse,rat,guinea pig ,rabbit , rat,cat, dog,
• Human models: it is first described by fieldman
and maibach. They includes determination of
percutaneous absorption by an indirect method of
measuring radioactivity in excreta following
topical application of the label drug 14c is
generally used for radio-labelling.
%dose absorbed =

48. KINETICS OF TRANSDERMAL
PERMEATION
– Knowledge of skin permeation kinetics is vital to the
successful development of transdermal therapeutic
systems. Transdermal permeation of a drug involves the
following steps:
1. Sorption by stratum corneum.
2. Penetration of drug through viable epidermis.
3. Uptake of the drug by the capillary network in the
dermal papillary layer.
The rate of permeation across the skin is given by:
dQ/dt = Ps ( Cd – Cr ) --------eq.1

50. • Where Cd and Cr are the concentration of the skin penetrant
in the donor compartment i.e. Ps is the overall permeability
coefficient of the skin tissue to the penetrant. This
permeability coefficient is given by the relationship:
Ps =ks dss /hs
• From equation (1) it is clear that a constant rate of drug
permeation can be obtained only when Cd >> Cr i.e.
the drug concentration at the surface of the stratum
corneum Cd is consistently and substantially greater
than the drug concentration in the body Cr. The
equation becomes:
dQ/dt= Ps Cd
• And the rate of skin permeation is constant provided
the magnitude of Cd remains fairly constant throughout
the course of skin permeation

51. REFERENCES
Controlled and Novel drug delivery edited by
N.K.Jain reprint 2007
www.sciencedirect.com
controlled drug delivery –concepts and advances –
by S.P.Vyas R.K.Khar