Transdermal drug delivery systems (TDDS) provide an alternative to oral administration and injections by delivering drugs through the skin. TDDS consist of a backing layer, drug reservoir, release liner, and adhesive layer. Drugs must have certain properties like molecular weight <1000 Daltons to permeate the skin. Permeation enhancers can temporarily increase skin permeability. The four main types of TDDS are membrane modulated, adhesive diffusion controlled, matrix dispersion, and microreservoir systems. The design objectives are to deliver drugs through the skin at therapeutic levels over time.

1. Transdermal Drug
Delivery System (TDDS)
Dr Samia Ghani
M.Phil Pharmaceutics

2. v Transdermal drug delivery offers an attractive
alternative to the oral administration and injection.
v Today about 74% of drugs are taken orally and are
found not to be as effective as desired.
vDrug delivery through the skin
(for systemic effect ) is commonly
known as TDD and differs from
traditional topical drug delivery.
2

3. Transdermal drug delivery system
• Transdermal drug delivery system is defined as “self
containing, discrete dosage forms which when applied
to the intact skin,deliver the drugs through the skin at a
controlled rate to the systemic circulation”.
• Transdermal delivery represents an attractive alternative
to oral delivery of drugs and is poised to provide an
alternative to hypodermic injection too.
3

4. TRANSDERMAL DRUG DELIVERY SYSTEM
• Trasns dermal drug delivery system has following components:
• Creams
• Ointments
• Pastes
• Plaster
• Poultice
• Paints
• Magmas
• Gel and Jellies
• Lotions
• Liniments
4

5. CREAMS:
• “Creams are semi solid emulsions for external application. Oil-in-
wateremulsions are most useful as water washable bases, whereas
water-in-oil emulsionsare emollient and cleansing.” 1
• “The term creamin pharmacy and medicine is applied to viscous
emulsions of semisolid consistency intended for application to the
skin or mucousmembrane. They may be of the water-in-oil (oily
creams) or oil-in water (aqueouscreams) type.” 2
5

6. OINTMENTS:
• “Ointments are those which may consist if a single fatty substance or
a mixture of fats, waxes and oils; in most cases medicament is also
present. Many ofthe official ointments are emulsions.” 1
• OR
“Ointments are semisolid preparations intended for external
application to the skin or mucous membranes. Ointments may be
medicated or unmedicated.Unmedicated ointments are used for the
physical effects they provide asprotectants, emollients, or lubricants.”
• OINTMENT BASES:
Ointment bases are classified by the USP into four groups:
1) Oleaginous Bases
2)Absorption Bases
3) Water-removable Bases
4) Water-soluble Bases
6

7. PASTES:
• “Dermatologic pastes are ointment-like preparations employed in
thepractice of dermatology. They are usually stiffer, less greasy and
more absorptivethan ointments due to a higher proportion of
powdered ingredients such asstarch, zinc oxide, calcium carbonate
and talc in the base.” 1
• “Pastes are semisolid preparations intended for application to the
skin. They generally contain a large proportion of solid material (such
as 25%) thanointments and therefore are stiffer.” 2
• “Pastes are stiffer preparation than ointments and contain a high
proportion of powder dispersed in a fatty base.” 3
7

8. PLASTER:
• “Plasters are solid or semisolid adhesive masses spread on a backing
of paper, fabric, mole skin, or plastic.” 1
• In the plasters the adhesive material is a rubber base or synthetic
resin. Plasters are applied to the skin to provide prolonged contact at
the site.Unmedicated plaster provides protection or mechanical
support at the site of application. Medicated plasters provide effects
at the site of application. They may be cut to size to conform to the
surface to be covered. Among the few plasters in use today is salicylic
acid plasters used on the toes for the removal of corns. The horny
layers of skin are removed by the karolytic action of salicylic acid. The
concentration of salicylic acid use in commercial corn plasters ranges
from 10 to 40%.
8

9. POULTICES:
• “A poultice is a viscous, pasty preparation for external use, usually
employed with the object of reducing inflammation and allaying pain
.e.g; Kaolin Poultice, BPC and Magnesium Sulphate. 1.
PAINTS:
• Paints are another group of liquid preparations for external
application, usually for circumscribed areas. They may be aqueous or
alcoholic solutions and sometimes are prepared with a collodion
basis to form a film on the skin. Compound tincture of Benzoin BPC is
also used as a basis for paints for the same reason (e.g. Compound
Podophyllin Paint, BPC).
• Paints should be dispensed in coloured fluted bottles, preferably
closed by means of glass stoppers. 2.
9

10. GELS:
• “Gels are defined as semisolid systems consisting of dispersions
made up of either small inorganic particles or large organic molecules
enclosing and interpenetrated by a liquid.”
OR
“Gels are also defined as semi rigid systems in which the movement of
the dispersing medium is restricted by an interlacing three-
dimensional network of particles or solvated macromolecule of the
dispersed phase.” 1
OR
“Lyophilic colloids such as gelatin, agar and pectin are soluble in hot
water and on cooling give rise to a semi-solid, jelly-like structure
termed as gel.”
10

11. JELLIES:
• “Jellies are a class of gels in which the structural coherent matrix
contains a high proportion of liquids, usually water. They usually are
formed by adding thickening agent such as tragacanth or
carboxymeythyle cellulose to an aqueous solution of a drug
substance. The resultant product is usually clear and uniformly
semisolid.”
• Jellies are subject to bacterial contamination and growth, so most are
preserved with antimicrobials. Jellies should be stored with tight
closure, since water may evaporate, drying out of product. 1
11

12. MAGMAS:
• “When the gel mass consists of floccules of small, distinct particles, the gel
• is classified as a two-phase system and frequently called a magma or a milk.”
1
LOTION:
• “This is fluid preparation for application to the skin or for use as washes,
• e.g. as mouth washes, gargles, solutions for rectal and vaginal irritation.” 2
• “Lotions are aqueous solutions or suspensions intended for application to
• the skin surface. If they contain insoluble solids in suspension, they are
sometimes referred to as ‘shake lotion. 3
12

13. LINIMENTS:
• “Liniments are liquid or semi liquid preparations intended for
application to the skin. Many of them are emulsions or simple
solutions.” 1
• “Liniment is an alcoholic or oleaginous solution applied by rubbing on
the skin for treatment of pain and stiffness of underlying
musculature.” 2
13

14. Øalso known popularly as ‘patches’.
Transdermal patches: are dosage forms designed
to deliver a therapeutically effective amount of
drug from the outside of the skin through its
layers into the blood stream.
14

15. 1. avoids the stomach environment;
2. no GI distress or other physiological
contraindications of the oral route exist;
3. easy to use, patches can compliance &
medical costs;
4. avoids the first-pass effect;
5. If a transdermal delivery system is used in place
of a needle, then medical waste can also be ,
again, healthcare costs.
15

16. 6. allows for the effective use of drugs with short
biological half-lives;
7. allows for the administration of drugs with
narrow therapeutic windows;
8. provides steady plasma levels of highly potent
drugs;
9. TDDS, especially simple patches, are easy to
use and noninvasive and patients like noninvasive
therapies.
16

17. 17

18. 1. drugs that require high blood levels cannot be
administered;
2. The adhesive used may not adhere well to all
types of skin;
3. drug or drug formulation may cause skin
irritation or sensitization;
4. the patches can be uncomfortable to wear;
5. and this system may not be economical for
some patients.
18

19. Disadvantages
• Many drugs especially drugs with hydrophilic structures
permeate the skin too slowly may not achieve therapeutic
level.
• The drug, the adhesive or other excipients in the patch
formulation can cause erythema, itching and local edema.
• The barrier function of the skin changes from one site to
another on the same person, from person to person and also
with age.
19

20. 20
q FDA (2005) announced that fentanyl td patches cause
narcotic overdose and deaths
qCause: manufacturing defect that allowed the gel
containing the medication to leak out of its pouch too
quickly, which could result in overdose and death.
qImprovement : use a matrix/adhesive
suspension (where the medication is
blended with the adhesive instead of
held in a separate pouch with a porous
membrane)

21. 21

22. oThe human skin is a readily accessible surface for
drug delivery.
oSkin of an average adult body
covers a surface of ~ 2 m² and
receives about 1/3 of the
blood circulating through
the body.
oHuman skin comprises of three
distinct but mutually dependent
layers :
22

23. Microscopically skin is a multilayered organ broadly composed of
three tissue layers :
§ The Epidermis
§ The Dermis
§ Subcutaneous fatty tissue.
23

24. 24

25. 25
Hairy skin develops hair
follicles and sebaceous glands
The most important layer is the
stratum corneum, or hairy layer,
which usually provides the rate-
limiting or slowest step in the
penetration process.

26. Principle mechanism is passive diffusion of drug
through the skin. macro-routes may comprise:
a.Transepidermal pathway b. Transfollicular pathway
26
Hair follicle
Sebaceous
gland Sweat gland

27. 27

28. Consideration of TDS
development
•Bioactivity of drug
•Skin characteristics
•Formulation
•Adhesion
•System design
28

29. Properties that influence
Transdermal delivery of the drug
•Release of the medicament from the vehicle.
• Penetration through the skin barrier.
• Skin structure and its properties
• The penetrating molecule and its physical-chemical
relationship to skin and the delivery platform
• The platform or delivery system carrying the penetrant
• The combination of skin, penetrant, and delivery system
•Activation of pharmacological response.
29

30. Factors influence transdermal
delivery
oBiological factors –
oSkin condition
oSkin age
oBlood flow
oRegional skin sites
oSkin metabolism
oSpecies differences
30

31. • Physicochemical factors –
• Skin hydration
• Temperature and pH
• Diffusion coefficient
• Drug concentration
• Partition coefficient
• Molecular shape and size
31

32. 32
1- Backing membrane,
2- Drug reservoir or matrix,
3- Release Liner,
4- Adhesive Layer.

33. 33
•
Ø BACKING MEMBRANE:
TDDSs have an occlusive backing membrane to protect the
system from environmental entry and from loss of drug from
the system or moisture from theskin.
•
Ø DRUG RESERVOIR OR MATRIX:
TDDSs have a drug reservoir or matrix system to store and
release the drug at the skin site.
•
Ø RELEASE LINER:
TDDSs have a release liner, which is removed before application
and enables drug release.
•
Ø ADHESIVE LAYER:
TDDSs have an adhesive layer to maintain contact with the skin
after application.

34. Basic components of TDDS
1. The drug
2. Polymer matrix
3. Permeation enhancers
4. Adhesive
5. Backing layer.
34

35. 1. Drug
The drug is in direct contact with release liner.
• Ex: Nicotine, Methotrexate, and Oestrogen.
• Some of the desirable properties of a drug for transdermal delivery:
• Should possess an adequate solubility in oil and water.
• Should have a molecular weight less than approximately 1000
daltons.
• Require a balanced partition coefficient to penetrate the stratum
corneum.
• Should have low melting point.
35

36. 2. Polymer matrix
These polymers control the release of the drug from the
drug reservoir.
• Natural polymers: shellac, gelatin, waxes, gums, starch
etc.
• Synthetic polymers: polyvinyl alcohol, polyamide,
polyethylene, polypropylene, Polyurea, polymethyl
methacrylate.
36

37. 3. Permeation enhancers
• Substances exist which temporarily diminish the
impermeability of the skin are known as accelarants or
sorption promoters or penetration enhancers.
Ø These include water, pyrolidones, fatty acids and
alcohols, azone and its derivatives, alcohols and glycols,
essential oils, terpenes and derivatives, sulfoxides like
dimethyl sulfoximide and their derivatives, urea and
surfactants
37

38. CHEMICAL ENHANCERS
• By definition, a chemical skin penetration enhancer
increases skin permeability by reversibly damaging or
altering the physicochemical nature of the stratum
corneum to reduce its diffusional resistance. Among the
alterations are increased hydration of the stratum
corneum, a change in the structure of the lipids and
lipoproteins in the intercellular channels through solvent
action or denaturation, or both.
38

39. IONTOPHORESIS
• Iontophoresisis delivery of a charged chemical compound across the
skin membrane using an electrical field. A number of drugs have
been the subject of iontophoretic studies; they include lidocaine;
dexamethasone; amino acids,peptides, and insulin; verapamil;and
propranolol. There is particular interest to develop alternative routes
for delivery of biologically active peptides. At present, these agents
are delivered by injection because of their rapid metabolism and
poor absorption after oral delivery. They are also poorly absorbed by
the transdermal route because of their large molecular size and ionic
character and the general impenetrability of the skin.
• However, iontophoresis-enhanced transdermal delivery has shown
some promise as a means of peptide and protein administration.
39

40. SONOPHORESIS
• Sonophoresis, or high-frequency ultrasound, is also being
studied as a means to enhance transdermal drug delivery.
Among the agents examined are hydrocortisone, lidocaine
and salicylic acid in such formulations as gels, creams, and
lotions. It is thought that high-frequency ultrasound can
influence the integrity of the stratum corneum and thus
affect its penetrability.
40

41. PERCUTANEOUS ABSORPTION MODELS
•Skin permeability and percutaneous absorption
have been the subject of numerous studies to
define the underlying principles and to optimize
transdermal drug delivery. Although many
experimental methods and models have been used,
they tend to fall into one of two categories, in vivo
or in vitro.
41

42. IN VIVO STUDIES
• In vivo skin penetration studies may be undertaken for one or more
of the following purposes:
• To verify and quantify the cutaneous bioavailability of a topically
applied drug.
• To verify and quantify the systemic bioavailability of a transdermal
drug
• To establish bioequivalence of different topical formulations of the
same drug substance
• To determine the incidence and degree of systemic toxicologic risk
following topical application of a specific drug or drug product
• To relate resultant blood levels of drug in human to systemic
therapeutic effects.
42

43. IN VITRO STUDIES
• Skin permeation may be tested in vitro using various skin
tissues (human or animal whole skin,dermis, or
epidermis) in a diffusion cell. Invitro penetration studies
using human skin are limited because of difficulties of
procurement, storage, expense, and variation in
permeation. Excised animal skins may also vary in quality
and permeation. Animal skins are much more permeable
than human skin.
43

44. 4. Adhesive
• Serves to adhere the patch to the skin for systemic drug
delivery of the drug
• Ex: Silicones, Polyisobutylene
44

45. 5. Backing layer
• Backing layer protects patch from outer environment.
• Ex: Cellulose derivatives, Polypropylene silicon rubber
45

46. Transdermal drug delivery devices
46

47. Types of TDDS
There are main four types of TDDS
• Membrane moderated system
• Adhesive diffusion controlled system
• Matrix dispersion system
• Micro reservoir system.
47

48. 48

49. 49

50. Matrix dispersion type TDDS
50

51. 51

52. Design objectives of TDDSs
• Deliver the drug to the skin for percutaneous absorption at
therapeutic levels at an optimal rate
• Contain medicinal agents having the necessary physicochemical
characteristics to release from the system and partition in to the
stratum corneum
• Occlude the skin to ensure one-way flux of the drug in to the stratum
corneum
• Have a therapeutic advantage over other dosage forms and drug
delivery systems
• Not irritate or sensitize the skin
• Adhere well to the patient’s skin and have size, appearance, and site
placement that encourage acceptance
52

53. 53

54. 54

55. 55

56. 56

57. GENERAL CLINICAL CONSIDERATIONS IN THE
USEOF TDDSs
• Percutaneous absorption may vary with the site of application. The
preferred general application site is stated in the package insert for
each product. The patient should be advised of the importance of
using the recommended site and rotating locations within that site.
Rotating locations is important to allow the skin beneath a patch to
regain its normal permeability after being occluded and to prevent
skin irritation. Skin sites may be reused after a week.
• TDDSs should be applied to clean, dry skin that is relatively free of
hair and not oily, irritated, inflamed, broken, or call used. Wet or
moist skin can accelerate drug permeation beyond the intended rate.
Oily skin can impair adhesion of the patch. If hair is present at the
intended site, it should be carefully cut; it should not be wet-shaved
nor should a depilatory agent be used, since the latter can remove
the outermost layers of the stratum corneum and affect the rate and
extent of drug permeation.
57

58. Transdermal controlled release products
Drug Trade Name Type of Device Indication
Scopolamine Transderm scop Reservoir Motion sickness
Nitroglycerine Transderm nitro Reservoir Angina
Nitro dur Monolithic
Nitro disc Monolithic
Estradiol Estraderm Reservoir Hormone
treatment
58

59. • 3. Use of skin lotion should be avoided at the application site
because lotions affect skin hydration and can alter the partition
coefficient between the drug and the skin.
• 4. TDDSs should not be physically altered by cutting (as in an
attempt to reduce the dose) since this destroys the integrity of
the system.
• 5. A TDDS should be removed from its protective package, with
care not to tear or cut into the unit. The protective backing
should be removed to expose the adhesive layer with care not
to touch the adhesive surface(which sometimes contains drug)
to the fingertips. The TDDS should be pressed firmly against the
skin site with the heel of the hand for about 10 seconds to
ensure uniform contact and adhesion.
59

60. • 6. A TDDS should be placed at a site that will not subject it to
being rubbed off by clothing or movement (as the belt line).
TDDSs generally may be left on when showering, bathing, or
swimming. Should a TDDS prematurely dislodge, an attempt
may be made to reapply it or it may be replaced with a fresh
system, the replacement being worn for a full period before it
is replaced.
• 7. A TDDS should be worn for the full period stated in the
product’s instructions. Following that period, it should be
removed and replaced with a fresh system as directed.
• 8. The patient or caregiver should be instructed to cleanse the
hands thoroughly before and after applying a TDDS. Care
should be taken not to rub the eyes or touch the mouth during
handling of the system.
60

61. •9. If the patient exhibits sensitivity or
intolerance to a TDDS or if un due skin irritation
results, the patient should seek re-evaluation.
•10. Upon removal, a used TDDS should be
folded in half with the adhesive layer together
so that it cannot be reused. The used patch,
which contains residual drug, should be placed
in the replacement patch’s pouch and discarded
in a manner safe to children and pets.
61

62. 62
vTransdermal drug delivery technologies are
becoming one of the fastest growing sectors within
the pharmaceutical industry.
vDespite some disadvantages, transdermal drug
delivery offers many advantages capable of
improving patient health and quality of life.
v 1st and 2nd generation TDDS
offer these advantages but are
limited in the scope of molecules
delivered through the skin.

63. PATCHES (NOT SYSTEMS)
• The Lidoderm (lidocaine) 5% patch consists of an adhesive
material containing 5% lidocaine,which is applied to a non
woven polyester felt backing and covered with a PET film
release liner. The release liner is removed just prior to
application. The patch is 10 cm × 14 cm and each patch
contains 700 mg of lidocaine in an aqueous base. The
base contains dihydroxy aluminum amino acetate,
disodium edentate, gelatin, glycerin, kaolin, methyl
paraben, polyacrylic acid, polyvinyl alcohol, propylene
glycol, propyl paraben, sodium carboxy methyl cellulose,
sodium poly acrylate, D-sorbitol, tartaric acid, and urea.
63

64. • This product is indicated to treat post herpetic neuralgia.
• The patch is applied to intact skin to cover the most painful
area.
• Depending upon the directions for use, the patient can
apply up to three patches, only once for up to 12 hours
within a 24-hour period.
• This patch may be cut with scissors into a smaller size prior
to the removal of the release liner.
• The patient should wash his/her hands prior to and after
handling the lidocaine patch and should avoid eye contact.
• After removal, the patch should be immediately disposed
of, and in such a way to avoid accidental exposure to
children and animals.
64

65. 65
Thank You