The document provides an introduction to transdermal drug delivery systems (TDDS). It discusses advantages like controlled delivery and avoidance of first-pass metabolism. Components are described, including rate-controlling polymers, drugs, permeation enhancers, adhesives and backing layers. Approaches to development include polymer membrane systems, polymer matrix systems, and adhesive or microreservoir systems. Recent approaches discussed are iontophoresis and electroporation, which use electric current to enhance skin permeation.

1. PRESENTED BY,
VINEETHA K
DEPT. OF PHARMACEUTICS
1st M.PHARM
NGSMIPS
1

2. CONTENTS
 INTRODUCTION
 ADVANTAGES
 DISADVANTAGES
 BASIC COMPONENTS
 APPROACHES USED IN DEVELOPMENT OF
TDDS
 REFERENCES
2

3. INTRODUCTION
• Definition:
Transdermal drug delivery is defined as a self
contained discrete dosage form, which when applied
to the intact skin, will deliver the drug at a controlled
rate to the systemic circulation.
3

4. BRIEF HISTORY OF TDDS.
 The NDDS may involve a new dosage form e.g., from thrice
a day dosage to once a day dosage form or developing a
patch form in place of injections.
 Throughout the past 2 decades, the transdermal patch has
become a proven technology that offers a variety of
significant clinical benefits over other dosage forms.
 Because transdermal drug delivery offers controlled release
of the drug into the patient, it enables a steady blood-level
profile, resulting in reduced systemic side effects and,
sometimes, improved efficacy over other dosage forms
4

5.  Transdermal drug delivery system was first introduced
more than 20 years ago.
 The technology generated tremendous excitement and
interest amongst major pharmaceutical companies in the
1980s and 90s.
 First transdermal patch was approved in 1981 to prevent
the nausea and vomiting associated with motion sickness,
the FDA has approved, throughout the past 22 years, more
than 35 transdermal patch products, spanning 13
molecules.
5

6. POTENTIAL BENEFITS OF TRANSDERMAL
DRUG DELIVERY (ADVANTAGES)
• Controlled delivery resulting in more reliable and
predictable blood levels.
• Easy to use.
• Avoids GIT absorption problems for drugs.
• Avoids First Pass hepatic metabolism of drugs.
• More improved and convenient, patient compliance.
• Self medication is possible.
• Reduces frequency of dosing.
• Rapid termination in case of toxicity is possible
• Maintains therapeutic level for 1 to 7 days.
6

7. DISADVANTAGES
• Daily dose of more than 10mg is not possible.
• Barrier function changes from person to person and within
the same person.
• Local irritation is a major problem.
• Drug with long half life can not be formulated in TDDS.
• Uncomfortable to wear.
• May not be economical.
• Heat, cold, sweating (perspiring) and showering prevent the
patch from sticking to the surface of the skin for more than
one day. A new patch has to be applied daily
7

8. Routes of drug absorption
through skin
8

9. ROUTES OF PERCUTANEOUS
PERMEATION.
1. Trans epidermal:
-passage of drugs through epidermis.
 Intracellular (transcellular pathway): in and across cell.
 Intercellular (paracellular pathway): between 2 cells.
2. Trans apendageal:
-through one or more appendages, hair
follicles, pores etc.
 Trans follicular(shunt pathway):
- avoids passing through stratum corneum,
pass through hair follicles and directly into sebaceous
gland.
 Trans eccrine:
-through the sweat gland.
9

10. COMPONENTS:
COMPONENT OF TRANSDERMAL DEVICE INCLUDE:
1) POLYMER MATRIX(RATE CONTROLLING POLYMER)
2) THE DRUG
3) PERMEATION ENHANCER
4) ADHESIVE
5) BACKING LAYER.
10

11. Basic components of Transdermal drug delivery
11

12. 1.RATE CONTROLLING POLYMER.
 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 or rate controlling
matrix.
LIST OF POLYMERS USED:
NATURAL POLYMERS: Cellulose derivatives, Zein,
Gelatin, Shellac, Waxes, Gums & Natural rubber
SYNTHETIC ELASTOMER : Polysiloxane, Silicon rubber,
Nitrile, Acrylonitryle, Butyl rubber, Styrene butadiene rubber.
SYNTHETIC POLYMER : Poly vinyl alcohol, Poly vinyl
chloride, Polyethylene, Poly propylene, Poly urea, PVP,
Polymethacrylate
12

13. 2.DRUG
For successful developing transdermal delivery, drug should
be chosen with great care physicochemical properties
1. Mol. wt. less than 1000 Daltons
2. Affinity for both lipophilic & hydrophilic phase
3. Drug should have low melting point.
13
BIOLOGICAL PROPERTIES:
It should be potent with daily dose of few mg/ day.
Half life of drug should be short.
Non irritant to skin.

14. 3.PERMEATION ENHANCERS
 Are compounds which are used to improve or alter the
permeability of skin by altering the barrier function of the
skin. Some of these compounds might alter the structure of
membrane.

14
THERE ARE FOUR GROUPS OF PERMEATION
ENHANCERS.:
1.Solvents: methanol, ethanol, DMSO, DMF(dimethyl
formamide), propylene glycol, glycerol.
2.Surfactants :
An ionic:dioctyl sulfosuccinate, sodium lauryl sulphate.
Cationic : sodium glycolate, sodium taurocolate.
Non ionic : pluronic CF 127,pluronic F-68.
3. Binary systems: propylene glycol
4. Misc. compounds: calcium thioglycolate

15. 4. ADHESIVES.
 It is an important component which is necessary for attachment
of TDDS.
 The fastening of all transdermal devices to the skin has been
done by using a pressure sensitive adhesive which can be
positioned on the face of the device or in the back of the device
and extending peripherally.
 Both adhesive systems should fulfill the following criteria
(i)Should adhere to the skin aggressively, should be easily removed.
(ii)Should not leave an unwashable residue on the skin.
(iii) Should not irritate or sensitize the skin.
15

16. 5.Backing membrane
They are flexible and provide a good bond to the drug
reservoir, prevent the drug from leaving the dosage form
through top.
It is an impermeable membrane that protects the product
during the use on the skin.
 Contains formulation throughout shelf-life and during
wear period
 Must be compatible with formulation (non adsorptive)
 Printable
E.g.: Metallic plastic laminate , plastic backing
16

17. 17
APPROACHES FOR THE
DESIGN OF TRANSDERMAL
DRUG DELIVERY SYSTEM.

18. 1. POLYMER MEMBRANE PERMEATION
CONTROLLED SYSTEM
18

19.  The drug reservoir is encapsulated in a shallow compartment.
 Bounded by drug impermeable metallic plastic laminate backing
layer .
 A thin layer of drug compatible, hypoallergenic adhesive
polymer. e.g. ethylene vinyl acetate copolymer.
 External surface of polymer membrane there is a thin layer of
pressure sensitive adhesive such as polyisobutylene.
 Adhesive layer is further protected by released liner of peel off
strip until it is ready to use.
 Drug release takes place by 0 order kinetics.
 Drug release controlled by controlling partition coefficient of
drug, diffusivity & thickness of polymer membrane.
 Dose dumping may occur if there is defect or tear in polymer
resulting in toxic effect.
19

20. 20
E.g.Transderm nitro: Nitroglycerine releasing trans dermal system
for once a day medication for angina pectoris – 2 layered patch.
a) A backing layer of aluminized plastic.
b) Drug reservoir containing nitroglycerine adsorbed on lactose,
colloidal silicon dioxide & silicone medical fluid.
c) Ethylene or vinyl acetate copolymer.
d) Silicon adhesive.
 Transderm Scop: Scopolamine-releasing transdermal system
for 72 hr, prophylaxis of motion sickness.
 Catapres -TTS: Clonidine releasing transdermal system for 7
day therapy of hypertension.
 Estraderm: Estradiol-releasing transdermal system for
treatment of menopausal syndrome for 3-4 days.

21. The intrinsic rate of the drug release from this type of drug delivery system
is defined by
21
Pm and pa respectively defined as:
Where,
 Km/r and ka/m are the partition coefficient for the interfacial
partitioning of the drug from reservoir to the membrane and from
the membrane to adhesive layer respectively.
 Dm and Da are diffusion coefficient and
 hm and ha are the thickness

22. 22
Substituting the pm and pa equation in equation 1
Which define the intrinsic rate of drug release from a
membrane moderated drug delivery system.

23. 2. POLYMER MATRIX DIFFUSION
CONTROLLED TDDS SYSTEM
23

24.  The drug reservoir is obtained by homogenous dispersion
of drug in hydrophilic or lipophilic rate controlling
polymer .
 Followed by cross linking of polymer chains.
 Or the drug & polymer is dissolved in common solvent
followed by evaporation of solvent in the mould under
vaccum or at elevated temperature.
 A medicated disc is obtained is glued onto an occlusive
base plate in a shallow compartment made from drug
impermeable backing layer.
 Adhesive is applied along the circumference of the patch to
form adhesive rim around the medicated disc.
 Advantage is no dose dumping.
 Drug release will not be 0 order.
24

25. 25
E.g. of this type of system is nitro- dur I and nitro- dur II. for continuous
transdermal fusion of nitroglycerine at a daily dose of 0.5 mg/cm2 for therapy
of angina pectoris.
Nitro dur II is modified version of I in which the drug is dispersed in acrylic
based polymer adhesive with a resinous cross linking agent which result in
much thinner and more elegant patch.
The rate of drug release from this type of system is defined as:
A is the initial drug loading dose dispersed in the polymer matrix and
Cp and Dp are the solubility and diffusivity of the drug in the polymer
respectively.
Since only the drug species dissolved in the polymer can release .

26. 3.ADHESIVE DISPERSION-TYPE
SYSTEM
26

27.  Drug reservoir is prepared by directly dispersing drug in rate
controlling adhesive polymer like polyacrylate.
 This medicated adhesive is coated onto a flat sheet of drug
impermeable metallic plastic laminate by solvent casting or as a
hot melt thereby producing a single drug reservoir layer.
 Simplest of all transderm patches & thinnest.
 E.g. : Nitrodur 2- contains nitroglycerin.
 This system can be modified by applying onto the medicated
adhesive layer thin layers of non medicated rate controlling
pressure sensitive adhesive layer to form adhesive diffusion
controlled system.
 E.g.: Frandol tape- isosorbide dinitrate.
27

28. 28
The rate of drug release in this system is defined by
where,
Ka/r is partition coefficient for the interfacial partitioning of the drug
from the reservoir layer to adhesive layer

29. 4.GRADIENT CONTROLLED TDDS
29
R1> R2>R3

30.  Contains several adhesive layer with varying loading level
of the drug to form a multilaminate adhesive device.
 Adhesive layer closer to the backing layer may contain
highest level of than the layer furthest away next to the skin
there by creating a gradient of drug loading a
multilaminate device forming a drug reservoir gradient
control system.
 Advantage is that they provide a zero order drug release.
 E.g. : Deponit system- nitroglycerin
30

31. 31
The rate of drug release from this drug reservoir gradient
controlled system is given by:
Thickness of the adhesive layer for drug molecules to
diffuse through increases with time h(t)

32. 5.MICRORESERVIOR TYPE OR
MICROSEALED DISSOLUTION
CONTROLLED SYSTEM
32

33.  Silicon elastomer the lipophillic polymer is used for
dispersion technique to form unleachable microscopic
sphere of drug reservoir.
 The quick stabilization occur by cross linking of the
polymer chain which produced medicated polymer disc
with a constant surface area and fixed thickness according
to requirement of drug release.
 Extra coating is available as a biocompatible polymer to
modify the mechanism and rate of drug release.
 A trans dermal therapeutic system is produced by
positioning the medicated disc at the centrally and
surrounded bit with an adhesive rim.
33

34. 34
It is successfully utilized in the preparation of nitro-disc, a nitroglycerine
releasing trans dermal therapeutic system used in angina pectoris.
This system followed zero order release of drug without the danger of
dose dumping.
The rate of release of drugs of the micro reservoir system is defined by,
Where, m=a/b is the ratio of the bulk of the elution medium over drug
solubility of the same medium and b is the ratio of drug concentration at
the outer edge of the polymer coating for the drug solubility in the same
polymer composition.
 n is the ratio of the drug concentration at the inner layer of the
interfacial barrier over drug solubility in the polymer matrix.

35.  Dl, Dp and Dd and hl, hp and hd; are diffusivities and thickness of liquid
layer surrounding the drug particle, polymer coating membrane
surrounding the polymer matrix and the hydrodynamic diffusion layer
surrounding the polymer coating .
 Kl, km and kp are the partition coefficient for the interfacial partitioning
of the drug from the liquid compartment to the polymer matrix, from
the polymer matrix to the polymer coating membrane and from the
polymer coating membrane to the elution solution respectively
 Sl and SP are the solubility of the drug in the liquid compartment and in
the polymer matrix respectively.
 The release of drug from this system can follow either a partition
control or matrix diffusion control process depending upon the relative
magnitudes of Sl and SP
35

36. 6. TRANSDERMAL DELIVERY OF THE
MACROMOLECULE
 Macromolecules such as Hormones, interferons, bioactive
peptides can be delivered by Trans dermal delivery system.
 The devices used for this purpose are divided in to two
categories….
1. Devices based on ethylene vinyl acetate copolymers (EVAc).
2. Devices based on silicone elastomer.
 This both the system utilize one common concept i.e.
 Matrix must have channel to facilitate the release of macro
molecule
 This device is used as implants
36

37. RECENT APPROACHES
1. IONTOPHORESIS:
 This method involves the application of a low level
electric current either directly to the skin or indirectly
via the dosage form in order to enhance permeation of
a topically applied therapeutic agent
 Built-in battery layer
 Comparable in size to a normal transdermal patch.
 e.g. : The Lectro Patch
 Treatment time : 20 min
 Recommended maximum current : 4mA
 Lidocaine (local anesthesia), dexamethasone (arthritis),
hydrocortisone (arthritis), acetic acid (calcified
tendinitis) etc.
37

38. IONTOPHORESIS
38

39.  The basic principle of iontophoresis is that a small electric
current is applied to the skin.
 This provides the driving force to primarily enable
penetration of charged molecules into the skin.
 A drug reservoir is placed on the skin under the active
electrode with the same charge as the penetrant.
 A indifferent counter electrode is positioned elsewhere on
the body.
 The active electrode effectively repels the active substance
and forces it into the skin
 . This simple electrorepulsion is known as the main
mechanism responsible for penetration enhancement by
iontophoresis
39

40. The technique offers number of advantages like:
 The benefits of bypassing hepatic first pass effect.
 Higher patient compliance
 Delivery of ionized and unionized drugs
 Enabling continuous or pulsatile delivery of drug
 Permitting easier termination of drug delivery
 Offering better control over the amount of drug delivered
 Restoration of the skin barrier function without producing
severe skin irritation
 Improving the delivery of polar molecules as well as high
molecular weight compounds
 Ability to be used for systemic delivery or local (topical)
delivery of drugs
40

41. 2.Electroporation:
 Transient high-voltage electrical pulses, to cause rapid permeabilization
of the stratum corneum through which large and small peptides,
oligonucleotides and other drugs can pass in significant amounts.
 This method involves the application of high voltage pulses to the skin
which has been suggested to induce the formation of transient pores.
High voltages (100 V) and short treatment durations (milliseconds) are
most frequently employed.
 Other electrical parameters that affect permeation rate include pulse
properties such as waveform, rate and number.
 The technology has been successfully used to enhance the skin
permeability of molecules with differing lipophilicity and size (i.e. small
molecules, proteins, peptides and oligonucleotides) including
biopharmaceuticals with molecular weights greater than 7kDA.23
41

42. 42

43. 3.Microneedle-based Devices
 The very first microneedle systems,
described in 1976, consisted of a
drug reservoir and a plurality of
projections (microneedles 50 to 100
mm long) extending from the
reservoir, which the stratum
corneum and epidermis to deliver
the drug.
 The ALZA Corp. has recently
commercialized a microneedle
technology named Macroflux which
can either be used in combination
with a drug reservoir or by dry
coating the drug on the
microprojection array24, the latter
being better for intracutaneous
immunization
43

44. 4.Abrasion:
 The abrasion technique involves the direct removal or
disruption of the upper layers of the skin to facilitate the
permeation of topically applied medicaments.
 Some of these devices are based on techniques employed by
dermatologists for superficial skin resurfacing (e.g.
microdermabrasion) which are used in the treatment of
acne, scars, hyperpigmentaion and other skin blemishes.
44

45. 5 .Needle-less Injection
 This is reported to involve a pain-free method of
administering drugs to the skin.
 Over the years, there have been numerous examples of
both liquid (Ped-O-Jet, Iject, Biojector2000, Medi-jector
and Intraject) and powder (PMED device formerly known
as Powderject injector) systems.
 The latter device has been reported to successfully deliver
testosterone, lidocaine hydrochloride and macromolecules
such as calcitonin and insulin.
45

46. 6.Laser Radiation
 This method involves direct and controlled
exposure of a laser to the skin which results in the
ablation of the stratum corneum without
significantly damaging the underlying epidermis.
 Removal of the stratum corneum using this
method has been shown to enhance the delivery of
lipophilic and hydrophilic drugs.
46

47. 7.Microporation
 Microporation involves the use of microneedles that are
applied to the skin so that they pierce only the stratum
corneum and increase skin permeability.
 Microneedles are needles that are 10 to 200 µm in height
and 10 to 50 µm in width.
 Microneedles do not stimulate the nerves, so the patient
does not experience pain or discomfort.
 They are usually drug coated projections of solid silicon or
hollow, drug filled metal needles.
47

48. 8. Sonophoresis:
 The application of high frequency ultrasound to enhance drug
penetration.
Examples:. Lidocaine, hydrocortisone, salicylic acid.
 Sonophoresis is a process that exponentially increases the absorption of
semisolid topical compounds (transdermal delivery) into the epidermis,
dermis and skin appendages.
 Sonophoresis occurs because ultrasound waves stimulate micro-
vibrations within the skin epidermis and increase the overall kinetic
energy of molecules making up topical agents.
 Application of ultrasound to the skin increases its permeability
(sonophoresis) and enables the delivery of various substances into and
through the skin
 Sonophoresis, or ultrasound, creates holes in the skin, and allows fluids
to travel into or out of the body.
 When sound is emitted at a particular frequency, the sound waves
disrupt the lipid bilayers. This method can be used for delivery of
steroids, systemic drugs such as Insulin and antigens for vaccination.
48

49. 49

50. REFERENCES.
1. Joseph RR, Vincent HLL. Controlled drug delivery. 2nd
Edn. Newyork : Marcel Dekker INC;1987.523-549 p.
2. Chein YW. Novel drug delivery system.2nd Edn.
Newyork : Marcel Dekker INC;1992.301-344 p.
3. Guy RH, Hadgraft J. Transdermal drug delivery
system.2nd Edn. Newyork : Informa health care;2003.1-
25 p.
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