Transdermal drug delivery systems (TDDS), are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin. It delivers a drug through intact skin at a controlled rate into the systemic circulation. Delivery rate is controlled by the skin or membrane in the delivery system.

1. TRANSDERMAL DRUG
DELIVERY SYSTEM
Presented By:
Miss. Sneha Gaurkar
Assistant Professor,
DRGIOP, Amravati
1

2. 01. INTRODUCTION
02. ADVANTAGES AND DISADVANTAGES
03.
IDEAL MOLECULAR PROPERTIES FOR
TRANSDERMAL DELIVERY.
04.
STRUCTURE OF SKIN AND BARRIERS.
 MECHANISM OF PERCUTANEOUS
ABSORPTION
 KINETIC OF TRANSDERMAL
PERMEATION
05. PENETRATION ENHANCER.
06. REFERENCES
CONTENT
2

3. What is TRANSDERMAL DRUG DELIVERY SYSTEM ?
 Transdermal drug delivery systems (TDDS) are topically administered medicaments in the form of patches,
which when applied to intact skin, allows the delivery of contained drugs into the systemic circulation via
permeation through skin layers at a predetermined and controlled rate.
 Transdermal patches typically involve a liquid, gel, solid matrix or pressure sensitive adhesive carrier into
which the drug is incorporated.
 This approach of drug delivery is more pertinent in case of chronic disorders (hypertension, diabetes)
which require long term dosing to maintain therapeutic drug concentrations.
3

4. ADVANTAGES OF TDDS
Self administration is possible.
Patience
compliance.
Termination of
therapy is easy at
any point of time.
Drugs with short
biological half life and
narrow therapeutic window
are suitable.
Avoidance of first
pass metabolism
Avoidance of gastro-
intestinal
incompatibility.
Ability to deliver
drug more
selectively to a
specific site.
Enhance therapeutic efficacy.
4

5. DISADVANTAGES OF TDDS
1
2
3
5
4
Local irritation/
uncomfortability.
Variation in barrier
function (age ,site).
Low permeability
limits.
Uncomfortable Wear
Molecular size restriction
(<500 Dalton ).
5

6. IDEAL MOLECULAR PROPERTIES FOR
TRANSDERMAL DELIVERY
3
2
1
6
5
4
The partition coefficient should be high if the molecular weight is > 600 daltons.
Low melting point of drug is desired (< 200°C).
Optimum partition coefficient is required for good therapeutic action.
An adequate solubility in liquid and water is necessary for better penetration of drug (1mg/ml).
The potent drug with dose of 10-15 mg/ day is desired.
The pH of the saturated solution should be in between 5 to 9.
6

7. SKIN
 Surface area of skin on an average adult body is 2 m2 or 3000 inch2.
 Thickness – 2.97 +/- 0.28 mm.
 Receives about 1/3rd of blood circulation of the body.
 Function – as a protective barrier.
- regulation of blood pressure.
- act as thermostat in monitoring body temperature.
- barrier against physical, chemical and microbial attacks.
- separates the underlying blood circulation network from the outside environment,
7

8. STRUCTURE OF SKIN AND BARRIERS
Three main layers of SKIN
DERMIS
HYODERMIS
1
2
3
EPIDERMIS
 Outer layer of skin is made up of
Stratified Squamous epithelial
cells.
 Epidermis is thickest in palms and
soles.
 Made up of regular network of
robust collagen fibers .
 Also called SUBCUTANEOUS TISSUE
 Lowermost layer
 Mainly used for fat storage.
 Stratum Corneum
 Stratum Lucidum
 Stratum Granulosum
 Stratum spinosum
 Stratum Basale
 Blood Vessels
 Sweat Glands
 Hair Follice
 Sebaceous Glands
 Adipose Tissue
 Artery
 Vein
8

9. EPIDERMIS
Stratum corneum
Consists of many layers of keratinized dead cells that are
flattened and non-nucleated; cornified.
Stratum lucidum
A thin, clear layer found only in the epidermis of the
lips,palm, and soles.
Stratum granulosum
Composed of one or more layers of granular cells that contain
fibers of keratin and shriveled nuclei.
Stratum spinosum
Composed of several layers of cells with centrally located,
large, oval nuclei and spine like process; limited mitosis
Stratum basale
Single layer of columnar or cuboidal basal cells. 9

10.  Water content of stratum corneum is around 20%.
 The moisture required for stratum corneum is around 10% (w/w) to maintain flexibility and
softness.
 It consists of Cermides and neutral lipids such as Sterols, free fatty acids and triglycerides.
 The stratum corneum behaves as a primary barrier to the percutaneous absorption.
EPIDERMIS
DERMIS
 Elastic properties.
 It is supplied by blood to convey nutrients, remove waste & regulate body temperature.
 Drug is well absorbed by this route.
 Upper portion of the dermis is formed into ridges containing lymphatics and nerve endings
10

11. SUBCUTANEOUS TISSUE
This is a sheet of the fat containing areolar tissue known as the superficial fascia attaching the
dermis to the underlying structures .
SKIN APPENDAGES
Sweat glands produces sweat of pH 4-6.8 & absorbs drugs, secretes proteins, lipids and
antibodies. Its function is to control heat.
HAIR FOLLICLES
They have sebaceous glands which produces sebum and includes glycerides, cholesterol and
squalene.
11

12. MECHANISM OF PERCUTANEOUS ABSORPTION
Principle mechanism is passive diffusion of drug through the skin.
a
b b
Hair follicle
Sebaceous gland
eccrine/sweat gland
(b).Diffusion through hair
follicles & eccrine/sweat
glands (called as
transfollicular or shunt
pathway absorption).
(a).Passage through
epidermis itself
(transepidermal
absorption).
MECHANISM OF PERMEATION
12

13. TRANSEPIDERMAL ABSORPTION :
Within the stratum corneum molecules can penetrate either Transcellularly or Intercellularly.
TRANSCELLULARLY means diffusion occurs through the cells of Stratum corneum.
o Polar compounds, ions/electrolytes pass through the Stratum corneum by Transcellularly.
INTERCELLULARLY means diffusion occurs through the intercellular lipoidal route.
o Intercellular space present between the Stratum corneum cells are filled with lipid rich
amorphous materials.
o Lipid molecules diffuse through Stratum corneum easily by intercellular route.
13

14. 14

15. • Eccrine glands are numerous, but absorption through them is not possible
because their orifices are tiny.
• Moreover they are either evacuated or so profusely active that molecules cannot
diffuse inwardly against the glands output.
15

16. Diffusion of drug through patch to skin surface
Partitioning of drug into Stratum Corneum Partitioning of the drug into Sebum
Diffusion through protein-lipid matrix of stratum
corneum
Diffusion through lipids in sebaceous pore
Partitioning into viable epidermis
Diffusion through cellular mass of epidermis
Diffusion through fibrous mass of upper dermis
Capillary uptake & systemic dilution of drug.
16

17. 17
Skin permeation kinetics is vital to the successful development of transdermal
therapeutic system.
Transdermal permeation of drug involve following
Steps –
1.Sorption by stratum corneum.
2.Penetration of drug through viable epidermis.
3.Uptake of drug by capillary network in dermal papillary layer.
Kinetic of transdermal permeation

18. 18
The rate of permeation across the skin (dq/dt) is given by –
dQ/dt = Ps (Cd-Cr)…………………….. (1)
Where ,
Cd and Cr - The concentration of skin penetrant in the donor compartment and in
the receptor compartment respectively,
Ps - Permeability coefficient.

19. 19
This permeability coefficient is given by the relationship:
Ps = Ks Dss / hs …………………………………………………………………………………..(2)
Where
Ks – Partition coefficient for the interfacial partitioning of the penetrate molecule from a solution
medium or a transdermal therapeutic system on to the stratum corneum
Dss – Apparent diffusivity for the steady state diffusion of the penetrate molecule through a
thickness of skin tissues
hs – Overall thickness of skin tissues
As Ks ,Dss and hs are constant under the given conditions , so the permeability coefficient (Ps )
for skin penetrate can be considered to be constant.
From Equation (1) , Constant rate of drug permeation can be obtained only when Cd >>> Cr
Then the Equation (1) becomes
dQ/ dt = Ps Cd ……………………………………………………………………...(3)

20. 20
The rate of skin permeation (dQ/dt) is constant provided the magnitude of Cd remains fairly
constant throughout the course of skin permeation.
For keeping Cd constant , the drug should be released from the device at a rate (Rr) that is
either constant or greater than the rate of skin uptake (Ra).
Since Rr is greater than Ra, the drug concentration on the skin surface (Cd) is maintained at a
level equal to or greater than the equilibrium solubility of the drug in the stratum corneum (Cs)
Therefore, the maximum rate of skin permeation is obtained and is given by the equation
(dQ/dt)m = Ps Cs ………………………………………………………(4)
From the above equation 4, the maximum rate of skin permeation depends on the skin
permeability coefficient (Ps) and its equilibrium solubility in the stratum corneum (Cs).

21. 21
PHYSICOCHEMICAL
FACTORS
ENVIRONMENTAL
FACTORS
BIOLOGICAL
FACTORS
 Skin Condition
 Skin Age
 Blood Supply
 Regional Skin Site
 Skin Metabolism
 Species
Difference
 Skin Hydration
 Temperature and PH
 Diffusion Coefficient
 Drug Concentration
 Partition Coefficient
 Molecular Size And
Shape
 Sunlight
 Cold Season
 Air Pollution
 Effect Of Heat
FACTORS INFLUENCING TRANSDERMAL DRUG DELIVERY

22. 22
BASIC COMPONENTS OF TRANSDERMAL DRUG DELIVERY SYSTEM
3
2
1
5
4
POLYMER MATRIX / DRUG RESERVOIR
MEMBRANE (Silicon rubber, Ethylene
vinyl acetate, Polyurethane)
DRUG
PERMEATION ENHANCERS
PRESSURE SENSITIVE ADHESIVES
(PSAs) (Polyisobutylene-based adhesives,
acrylics,Silicon-based PSAs, Hydrocarbon
resins)
BACKING LAMINATES (Vinyl, Polyethylene,
polyester films, Aluminium films)
RELEASE LINER (Polyethylene, Polyvinyl
chloride, Paper fabrics)
OTHER EXCIPIENTS LIKE PLASTICIZERS
AND SOLVENTS
6
8
7

23. 23
PENETRATION
ENHANCER

24. 24
1
2
3
Substance that facilitate the permeation through mucosa are referred as
penetration enhancer
 Increases the absorption of penetrant through the skin.
 Synonyms:
Absorption promoter and Sorption accelerants.
 Increases the permeability of the Stratum Corneum so as to attain higher
therapeutic levels of the drug candidate.
WHAT IS PENETRATION ENHANCERS ?

25. 25
o Non-toxic, non-irritating and non-allergic
o Rapid working
o Predictable and reproducible duration of action
o No pharmacological activity within the body
o Work unidirectional
o Compatible with both excipients and drugs
o Cosmetically acceptable
DESIRABLE PROPERTIES FOR IDEAL PENETRATION
ENHANCERS

26. 26
• To increase the delivery of ionizable drugs.
Example: Timolol maleate etc.
• To deliver the impermeable drugs.
Example: Heparin etc.
• To maintain level of drug into blood stream.
• To improve the efficacy of less potent drugs with higher dose.
Example : Oxymorphone
• To deliver the drugs having high molecular weight like peptide and hormones
• To decrease lag time of transdermal drug delivery system.
USES OF PENETRATION ENHANCERS

27. 27
1) Most drugs penetrate at rates sufficiently high for therapeutic
efficiency by using penetration enhancers.
2)It is useful for unabsorbable drugs to facilitate their absorption
through skin.
3)It can improve transdermal absorption of topical preparation.
4)No adverse effect on skin.
5)Do not affect zero order skin permeation profile of skin.
6)The terpenes like limonene in propylene glycol solution are effective
penetration enhancer for cytotoxic drugs.
MERITS OF PENETRATION ENHANCERS

28. 28
DEMERITS OF PENETRATION ENHANCERS
1.The effective
concentration varies
from drug to drug.
2.The uses of
different penetration
enhancer with various
concentrations are
restricted completely.
3. Physicochemical
properties of
enhancers are also
affecting the side
effects in the body.

29. 29
ENHANCE PERMEATION ACROSS SKIN
CHEMICAL PHYSICAL
1.Sulphoxides and similar
chemicals
2.Azone
3.Pyrrolidones
4.Fatty acids
5.Essential oils, terpenes
and terpenoids
6.Oxazolidodienes
7.Urea
A] ELECTRICALLY
BASED TECHNIQUES
B] STRUCTURED BASED
TECHNIQUE
C] VELOCITY BASED
TECHNIQUE
1. Iontophoresis
2. Electroporation
3. Ultrasound
(sonophoresis)
4. Photochemical
waves
5. Laser Ablation
Microneedles Jet-propelled
particles

30. 30
CHEMICAL PENETRATION ENHANCEMENT
MECHANISM OF CHEMICAL PENETRATION ENHANCEMENT
1. Disruption of the highly ordered structure of stratum corneum lipid.
Ex. Oleic acid and terpenes at high loadings pool with lipids, phase separate and form
permeable pores which allow easier access to the viable epidermis for polar molecules
2. Interaction with intercellular protein.
Ex: lonic surfactants, decyl methyl sulphoxide and DMSO
3. Improved partition of the drug, co-enhancer or solvent into the stratum.
Ex. Ethanol increases penetration of nitroglycerin & estradiol.

31. 31
PHYSICAL PENETRATION ENHANCEMENT
1. IONTOPHORESIS :-
It acts by repulsion effect between charged electrode and solute (drug reservoir)
Applied electric current of 0.5mA/cm2
Low M.W (‹500 Da)
Ex- Lidocaine, metoclopramide plus hydrocortisone, vincristine etc,.

32. 32
2. ELECTROPORATION:-
 Process involves the application of large transmembrane voltages caused by
electrical pulses (10μs–100ms).
 It cause formation of transient pores in the membrane that allow the passage
for drug.
 Induce steady-state transport through skin with in minute.
 Controllable through manipulation of electrical pulse.

33. 33
3. ULTRASOUND (OR SONOPHORESIS):-
 Sonophoresis is the use of ultrasound to drive molecules into and across skin.
 The vibrations cause small spaces to open between the skins cells.
 Deliver drug in low frequency range 20 kHz.

34. 34
4. PHOTOCHEMICAL WAVES:-
 It also known as laser generated stress waves
 PWs are the pressure pulses produced by ablation of a material target.
 It have not much more attention.

35. 35
5. LASER ABLATION:-
 The use of lasers to remove the stratum corneum barrier by controlled ablation.
 It is reported that use of LAs on pig Stratum corneum- hydrocortisone.

36. 36
STRUCTURED-BASED TECHNIQUE:-
Microneedle:-
 They create a physical pathway through the upper epidermis to increase skin permeability.
 Made up of silicon
 Silicon needles individual measuring about 150μm in length and 80μm base diameter and fabricated
on array of 3x3 mm (400 needles).

37. 37
Current commercial MNs-based products
(a) Intanza® and (b) MicronJet®.

38. 38
VELOCITY BASED TECHNIQUE-
Jet-propelled particles:-
 It propel the drug into the skin.
 High velocity jet (100m/s) of compressed gas (helium).

39. 39
VARIOUS APPROACHES TO TRANSDERMAL DEVICES
Membrane Permeation Controlled TDDS
Adhesive Dispersion Type TDDS
Polymer Matrix Diffusion Controlled TDDS
Micro Reservoir type TDDS
1
2
3
4

40. 40
Membrane Permeation Controlled TDDS
• In this type of TDDS, drug reservoir is sandwiched between drug impermeable
backing membrane and rate controlling membrane.
• The drug release only through the rate controlling membrane. It can be microporous
or porous.

41. 41
Adhesive Dispersion Type TDDS
• In this type of drug reservoir is prepared by directly dispersing the drug in an
adhesive polymer.
• Then this medicated adhesive polymer is spread over a flat sheet of drug impermeable
backing membrane.
• The drug reservoir layer is then covered by a non-medicated rate controlling polymer
of constant thickness to produce an adhesive diffusion controlling DDS.

42. 42
Polymer Matrix Diffusion Controlled TDDS
• Drug reservoir is prepared by dispersing the drug homogenously in a hydrophilic and lipophilic
polymer matrix.
• The resultant medicated polymer is then moulded on a medicated disc of defined surface area and
thickness.
• The drug reservoir can also be formed by dissolving the drug and polymer in a common solvent and
then evaporation of solvent at an elevated temperature.
• This drug reservoir containing polymer disc is then pasted over a base plate containing drug
impermeable backing membrane.

43. 43
Micro Reservoir Type TDDS
• A drug reservoir is formed by first suspending the solid drug in an aqueous solution of water
soluble polymer.
• This drug suspension is homogenously dispersed in a lipophilic polymer by highly energy
dispersion technique.
• This forms the microscopic spores of drug reservoir which are supported over an occlusive pad
and are thermodynamically unstable.
• It can be further coated with a layer of biocompatible polymer to improve the drug release.

44. 44
REFERENCES-
1. Chein, Y W, 1992, Novel Drug Delivery System, 2nd edition, vol-14, Marcel
Dekker , New York, page no. - 301-314.
2. Controlled & Novel drug delivery by N.K.Jain
3. Artificial “Penetration enhancers” by Ardian C. Williams, Brian W.
Barry; Adv. Dr. Delivery Reviews.
4. Internet sources.