transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream
2. Transdermal drug delivery can deliver drugs via
the skin portal to systemic circulation at a
predetermined rate and maintain clinically
effective concentrarion over a prolonged period
of time.
3. Percutaneous Absorption
The absorption of substances from
outside the skin to positions beneath the skin,
including entrance into the blood stream
Penetration of the Skin by Drugs
Drugs may penetrate intact skin after
topical application (a)through the walls of the
hair follicles,(b) through the sweat glands or the
sebaceous glands, (c) or between the cells of the
horny layer.
4. Are designed to support the passage of drug
substances from the surface of the skin, through
its various layers, and into the systemic
circulation.
5. The main route for the penetration of drug is
generally through the epidermal layers, rather
than through the hair follicles or the gland ducts,
because the surface area of the latter is rather
minute compared to the area of the skin.
6. The percutaneous absorption of a drug
generally results from direct penetration
of the drug through the stratum
corneum.
Permeation of the laminate barriers in stratum
corneum can occur by diffusion via:
1. Transcellular penetration (across the
cells)
2. Intercellular penetration (between the cells)
3. Transappendageal penetration (via hair
follicles, sweat and sebum glands, and
pilosebaceous apparatus)
8. STRUCTURE OF SKIN
Epidermis:
The outer layer of skin is made up of Stratified
Squamous epithelial cells.
Epidermis is thickest in palms and soles.
The stratum corneum forms the outer most layer (10-
15µm thick ) which consists of many layers of compacted
, flattened, dehydrated keratinized cells.
Keratin contains cells called as Corneosites.
Stratum corneum layer forms permeability barrier for
external environment. 8
9. DERMIS:
The dermis is made up of regular network of robust
collagen fibers of fairly uniform thickness with regularly
placed cross striations .
This network or the gel structure is responsible for the
elastic properties of the skin.
It is supplied by blood to convey nutrients, remove waste &
regulate body temp.
Drug is well absorbed by this route.
Upper portion of the dermis is formed into ridges
containing lymphatics and nerve endings.
9
STRUCTURE OF SKIN
10. 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. 10
STRUCTURE OF SKIN
11. MECHANISM OF ABSORPTION THROUGH SKIN
Mechanism involved is passive diffusion
This can be expressed by FICK’s LAW of DIFFUSION
dq = D K A ( c1 – c2 )
dt h
dq /dt = rate of diffusion
D = diffusion co-efficient
K = partition co- efficient
A = surface area of membrane
H = thickness of membrane
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12. ROUTES OF DRUG ABSORPTION THROUGH SKIN
Trans follicular route
Trans epidermal route
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13. ROUTES OF DRUG ABSORPTION THROUGH SKIN
Trans follicular route:
Fractional area available through this route is 0.1 %
Human skin contains 40-70 hair follicles, 200 to 250
sweat glands on every sq.cm. of skin area.
Mainly water soluble substance are diffused faster
through appendages than that of other layers.
Sweat glands and hair follicles act as a shunt i.e. easy
pathway for diffusion through rate limiting ST corneum.
13
14. ROUTES OF DRUG ABSORPTION THROUGH SKIN
Trans Epidermal route
Epidermal barrier function mainly resides in horny layer
The viable layer may metabolize, inactivate or activate a
prodrug.
Dermal capillary contains many capillaries so residence
time of drug is only one minute.
Within stratum corneum molecule may penetrate either
transcellularly or intercellular.
Intracellular region is filled with lipid rich amorphous
material.
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16. Avoidance of first pass metabolism
Avoidance of gastro intestinal incompatibility
Predictable and extended duration of activity
Provides utilization of drugs with short biological half
lives
Narrow therapeutic window
Improving physiological and pharmacological response
17. Avoiding the fluctuation in drug levels
Maintain plasma concentration of potent drugs
Greater patient compliance due to elimination of
multiple dosing profile
Ability to deliver drug more selectively to a specific site
Provide suitability for self administration
Enhance therapeutic efficacy
18. The drug must have some desirable physicochemical
properties for penetration through stratum corneum.
The transdermal delivery will be very difficult, if the
drug dose required is more than 10 mg/day for their
therapeutic application.
Only relatively potent drugs are suitable candidates for
TDDS.
The barrier function of the skin changes from one site to
another on the same person, from person to person and
with age.
21. Chemical Enhancers
•Increasing the drug permeability through the skin by
causing reversible damage to the SC.
•Conditioning the SC to promote drug diffusion.
•Increasing the partition coefficient of the drug to
promote its release from the vehicle into the skin.
Materials used to enhance absorption: surfactants,
azone,dimethylsulfoxide(DMSO),dimethylacetamide,
alcohol, acetone, propylene glycol, and polyethylene
glycol.
22. Physical Enhancers: Iontophoresis
Sonophoresis
Iontophoresis involves the delivery of charged
chemical compounds across the skin membrane using
an applied electrical field.
Examples: lidocaine, amino acids/peptides/insulin, verapamil,
and propanolol
Sonophoresis, or high-frequency ultrasound, is also
being studied as a means to enhance transdermal drug
delivery
Examples: hydrocortisone, lidocaine, and salicylic acid in such
formulations as gels, creams and lotions
23. A PSA maintains an intimate contact between
patch and the skin surface. It should adhere with
not more than applied finger pressure, be
aggressively and permanently tachy, and exert a
strong holding force. For example polyacrylates,
polyisobutylene and silicon based adhesives.
24. The primary function of the backing laminate is to
provide support.Backing layer should be chemical
resistant and excipient compatible because the
prolonged contact between the backing layer and the
excipient may cause the additives to leach out or may
lead to diffusion of excipient,drug or penetration
enhancer through the layer.
EXAMPLES of some backing material are Aluminium
vapor coated layer,polyethylene,PVC films etc.
25. During storage the patch is covered by a protective liner
that is removed and discharged immediately before the
application of the patch to skin. It is therefore regarded as
a part of the primary packaging material rather than a part
of dosage form for delivering the drug.
Typically, 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.
28. FACTORS AFFECTING
TRANSDERMAL PERMEABILITY
Physico chemical properties of parent molecule
Solubility and partition co- efficient
pH condition
Penetrant concentration
Physico chemical properties of drug delivery system
Release characteristic
Composition of drug delivery system
Permeation enhancer used
28
29. Physiological and pathological condition of skin
Lipid film
Skin hydration
Skin temperature
Effect of vehicle
Pathological injury to skin
Biological factors
Skin age
Thickness of S. Corneum
Skin condition
29
30. Solubility and partition co- efficient:
Solubility of a drug influences its ability to penetrate
the skin.
pKa is index of solubility of drug in vehicle and ST
corneum has influence on transfer of drug from vehicle
to skin.
Drug solubility determines concentration presented to
absorption site which will effect rate and extent of
absorption.
Skin permeation can be enhanced by increasing
lipophilic character of drug, so that drug penetrates
through STC but not through epidermis due to decreased
water solubility.
Drug which is lipid & water soluble is favored.
30
31. pH & penetration concentration:
Moderate pH is favorable because if solutions with high
or low pH will result in destruction to the skin.
Higher the concentration of the drug in vehicle faster
the absorption.
At higher concentrations than solubility the excess solid
drug will function as a reservoir and helps to maintain a
constant drug constitution for prolonged period of time.
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34. Thickness of the patch
The thickness of the
drug prepared patch is measured by using a
digital micrometer at different point of patch
and determines the average thickness and
standard deviation for the same to ensure the
thickness of the prepared patch
34
35. Content uniformity test
10 patches are selected and
content is determined for individual patches. If 9 out of
10 patches have content between 85% to 115% of the
specified value and one has content not less than 75% to
125% of the specified value , then transdermal patches
pass the test of content uniformity. But if 3 patches have
content in the range of 75% to 125%,then additional 20
patches are tested for drug content. If these 20 patches
have range from 85% to 115%, then the transdermal
patches pass the test
35
36. Drug content determination
An accurately weighed
portion of film (above 100 mg) is dissolved in 100 mL
of suitable solvent in which drug is soluble and then the
solution is shaken continuously for 24 h in shaker
incubator. Then the wholesolution is sonicated. After
sonication and subsequent filtration, drug in solution is
estimated spectrophotometrically by
appropriate dilution
36
37. Moisture content:
The prepared films are weighed individually and
kept in a desiccators containing calcium chloride at
room temperature for 24 h. The films are weighed
again after a specified interval until they show a
constant weight. The percent moisture content is
calculated using following formula.
Initial wt. – Final Wt.
% Moisture content = ---------------------------------
X100
Final weight
37
38. Moisture Uptake:
Weighed film sare kept in a desiccator at room temperature
for 24 h. These are then taken out and exposed to 84%
relative humidity
using saturated solution of Potassium chloride in a desiccator
until a constant
weight is achieved. % moisture uptake is calculated as given
below.
Final weight – Initial weight
% moisture uptake =---------------------------------- X 100
Initial weight
38
39. To determine tensile
strength , polymeric
films are sandwiched
separately by corked
linear iron plates
One end of the films is kept
fixed with the help of an
iron screen and other end is
connected to a freely
movable thread over a
pulley
1 2 3 4 5 6 7 8 9 10 11 12
Weight
PulleyFilm
Thread
40. The weights are added
gradually to the pan
attached with the hanging
end of the thread
A pointer on the thread
is used to measure the
elongation of the film.
The weight just
sufficient to break the
film is noted
Tensile strength= F/a.b (1+L/l)
F= is the force required to break
a=width of film
b=thickness of film;
L= length of film
l=elongation of film at break point.
43. •The highest selling transdermal patch in the United
States is the nicotine patch, which releases nicotine in
controlled doses to help with cessation of tobacco
smoking.
•Nitroglycerin patches are sometimes prescribed for the
treatment of angina in lieu of sublingual pills.
•The anti-hypertensive drug Clonidine is available in
transdermal patch form.
•Transdermal form of the MAOI selegiline, became the
first transdermal delivery agent for an antidepressant.
44. 1. Clonidine - Catapress -TTS
Four-layered patch:(1) backing layer of
pigmented polyester film (2) drug reservoir of
clonidine, mineral oil, polyisobutylene, and colloidal
silicon dioxide, (3) a microporous polypropylene
membrane controlling the rate of drug delivery, and (4)
an adhesive formulation of agents
Uses: antihypertensive clonidine at a constant rate
for 7 days, once a week dosing in the upper arm
or torso.
45. 2. Estradiol - Estraderm
Four layered patch: (1) transparent polyester film,
(2) drug reservoir of estradiol and alcohol gelled
with hydroxypropyl cellulose, (3) an ethylenevinyl
acetate copolymer membrane, and (4) an
adhesive formulation of light mineral and
polyisobutylene.
Uses: design to release 17 B-estradiol continuously.
Applied twice weekly over a cycle of 3 weeks.
The patch is generally applied to the abdomen,
altering sites with each application.
46. 3. Nicotine - Nicotrol
Multi-layered rectangular patch: (1)outer backing of
laminated polyester film, (2) rate-controlling adhesive,
nonwoven material, and nicotine, (3) disposable liner
removed prior to use - Aid in smoking cessation
programs.
47. It is used as a temporary aid for smoking-cessation programs. It
helps to control the symptoms of nicotine withdrawal
(irritability, headache, fatigue, insomnia) and thus helps you to
concentrate on overcoming the psychological and behavioral
aspects of your smoking habit.
48. 4.Nitroglycerin - Nitro - Dur
Nitroglycerin in a gel like matrix composed of
glycerin, water, lactose, polyvinyl alcohol, povidone
and sodium citrate sealed in a polyester foil
polyethylene laminate.
Use: to provide controlled release of nitroglycerin
continuously for a 24 hour period. Patches are
applied to inner part of upper arm, shoulders, or
chest.
49. This is a band-aid-like patch inserted on your gum to
numb it before an injection