TDDS, Anatomy of Skin, Advantages and disadvantages,Permeation of Drug Molecule through Skin, Factors affecting Transdermal Permeation, Design of transdermal system, Evaluation of TDDS

1. TRANSDERMAL DRUG
DELIVERY SYSTEM
(TDDS)
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PRESENTED BY:
• JYOTI NAUTIYAL
• M.PHARM. 2ND YEAR
• PHARMACEUTICS
• SGRRITS

2. CONTENT
• Introduction
• Advantages-Disadvantages
• Anatomy of Skin
• Permeation of Drug Molecule through Skin
• Factors affecting Transdermal Permeation
• Design of transdermal system
• Evaluation of TDDS
• Marketed Product
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3. INTRODUCTION
• TDDS are topically administered medicaments in the form of patches that deliver drugs
for systemic effects at predetermined and controlled rate.
• Transdermal patch is an adhesive patch, that has a coating of medicine (drug), that is
placed on the skin to deliver specific dose of the medicine, into the blood over a period
of time.
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4. ADVANTAGES
• Easy to use.
• Avoid GIT absorption problems for drugs.
• Avoids hepatic metabolism of drugs.
• More improved and convenient patient compliance.
• Rapid termination in case of toxicity is possible.
• Self medication is possible.
• Reduces frequency of dosing.
• Maintains therapeutic level for 1 to 7 days.
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5. DISADVANTAGES
• Drug that require high blood levels cannot be administered or if drug dose required for
therapeutic value is more than 10-25 mg/day, the transdermal delivery will be very
difficult. Daily doses of less than 5mg/day are preferred.
• Local irritation at the site of administration such as erythema, itching and local edema
may be caused by the drug, adhesive or other excipients in TDDS.
• Difficulty of permeation of the drug through human skin –barrier function of the skin.
• Adhesive may not adhere well to all types of skin.
• TDDS cannot achieve high drug concentration.
• Drugs of large molecular size cannot be developed for TDDS.
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6. ANATOMY OF SKIN
• Skin is a multilayered organ
• It is composed of three tissue layers -
A. The epidermis
B. The dermis
C. Subcutaneous fat tissue 6

7. A. EPIDERMIS
• Outer layer of the skin
• Composed of stratified squamous epithelial cells.
• Microscopic section of epidermis shows four main parts -
1. Stratum corneum
2. Stratum lucidum
3. Stratum granulosum
4. Stratum spinosum
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8. B. DERMIS
It is composed of network of collagen & elastic fibers embedded in a mucopolysaccharide matrix,
which contain blood vessels, lymphatic & nerve endings, there by providing physiological support
for epidermis.The dermis is the layer of tissue that is Deeper and Thicker than epidermis.
C. SUBCUTANEOUS TISSUE
• It is also called as Hypodermis.
• It is made up of loose connective tissue, including Adipose tissue.
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9. PATHWAYS OF DRUG PENETRATION
1- Transcellular route
2- Intercellular route
3- Transappendageal route
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10. PERMEATION OF DRUG MOLECULE
THROUGH SKIN
• Mechanism involved is Passive Diffusion .
• This can be expressed by Fick’s First law of Diffusion-
dq/dt = D K A ( c1 – c2 )/h
dq /dt = rate of diffusion
D = diffusion co-efficient
K = partition co- efficient
A = surface area of membrane
H = thickness of membrane
c1 – c2 = Conc gradient across the skin
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11. FACTORS THAT INFLUENCE TRANSDERMAL
DRUG DELIVERY
A. SKIN CONDITION
• Thickness of stratum corneum
• Presence of hair follicle
• Trauma
• Hydration of skin
• Age
B. EXTERNAL FACTORS
• Environmental humidity and temperature
• Exposure to chemicals
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12. DESIGN OF TRANSDERMAL SYSTEM
COMPONENTS OF TRANSDERMAL PATCH-
• The main components to a transdermal patch are:
I. Liner - Protects the patch during storage. The liner is removed prior to use.
II. Drug - Drug solution in direct contact with release liner
III. Adhesive - Serves to adhere the components of the patch together along with adhering the
patch to the skin
IV. Membrane - Controls the release of the drug from the reservoir and multi-layer patches
V. Backing - Protects the patch from the outer environment
VI. Permeation Enhancer - These are permeation promoters for drugs, which increases
delivery of drug.
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13. COMPONENTS OF TRANSDERMAL PATCH
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14. CLASSIFICATION OF TDDS
A. RATE PROGRAMMED SYSTEM
• The four main types of transdermal
patches are-
1. Drug in Adhesive Type
2. Drug in Matrix Type
3. Drug in Reservoir Type
4. Drug in Microreservoir Type
B. PHYSICAL STIMULI ACTIVATED
SYSTEM
• It mainly include –
1. Iontophoresis
2. Electroporation
3. Sonophoresis
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15. A. Reservoir Type
• It involves the system in which the drug is enclosed within a drug reservoir.
• The drug reservoir is encapsulated in a shallow compartment moulded from a drug impermeable
metallic – plastic lamination whilst the drug delivery side is covered by controlling polymeric
membrane.
• The drug molecules are released only through the rate controlling membrane.
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16. B. Matrix Type
• It is formed by homogenously dispersing the drug in a mixture of hydrophilic –
Lipophilic polymer{matrix} & the medicated polymer is moulded on the medicated disc
of defined surface area & thickness .
• It is then glued over an occlusive base plate consisted of compartment fabricated using
an impermeable plastic backing.
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17. C. Adhesive Type
• It is prepared by directly dispensing the drug in an adhesive polymer & then spreading
the medicated adhesive by solvent film casting method over a flat sheet of drug
impermeable metallic or plastic backing membrane, this forms a thin drug reservoir
layer.
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18. D. Microreservoir Type
• It has features of both reservoir & matrix dispersion type drug delivery system.
• The drug reservoir is formed by suspending the drug solid in an aq. Solution of
water soluble polymer.
• The drug suspension is dispersed homogenously in a Lipophilic polymer, by high
shear mechanical agitation to form thousands of microspheres of drug.
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20. EVALUATION PARAMETERS
A. Percentage Moisture uptake:
• Weighed films are to be taken in a desicator at room temperature for 24 hrs. These are
then taken out and exposed to 84% relative humidity using saturated solution of
potassium chloride in a desicator until a constant weight is achieved. Percentage
moisture uptake is calculated as given below.
Percentage moisture uptake=Final weight- Initial weight X 100
Initial weight
B. Folding Endurance
• A strip of specific area is to be cut evenly and repeatedly folded at the same
place till it broke. The number of times the film could be folded at the same
place without breaking gave the value of the folded endurance. 20

21. C. Skin irritation study
Skin irritation testing can be performed on healthy rabbits (average weight 1.2 to 1.5
kg). The dorsal surface of the rabbit is to be cleaned and remove the hair from the
clean dorsal surface by shaving and clean the surface by using rectified spirit and the
representative formulations can be applied over the skin. The patch is to be removed
after 24 hr and the skin is to be observed and classified into 5 grades on the basis of
the severity of skin injury.
0- No Erythema
1- Slight Erythema (light pink)
2- Moderate Erythema (dark pink)
3- Moderate to severe Erythema (light red)
4- Severe Erythema (extreme redness) 21

22. D. In vitro drug release studies:
• The paddle over disc method can be employed for assessement of the release of the drug from
the prepared patches. Dry films of known thickness is to be cut into definite shape, weighed,
and fixed over a glass plate with an adhesive. The glass plate was then placed in a 500ml of
the dissolution medium or phosphate buffer (pH 7.4), and the apparatus was equilibrated to
32+ 0.5 ˚C. The paddle was then set at a distance of 2.5 cm from the glass plate and operated
at a speed of 50 rpm. Samples can be withdrawn at appropriate time intervals upto 24hrs and
analysed by UV spectrophotometer. The experiment is to be performed in triplicate and the
mean value can be calculated.
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23. E. In vitro skin permeation studies:
• In-vitro permeation study can be carried out by using Franz Diffusion cell
with an effective permeation area and receptor cell volume of 1.0 cm2 and 10 ml
respectively.
• The temperature is maintained at 32˚C. the receptor compartment is filled with 10
ml phosphate buffer solution and is constantly stirred in a magnetic stirrer at
100rpm.
• The skin is then mounted on receptor compartment with stratum corneum side
facing upward into the donor compartment
• The transdermal patch is then applied on the skin in donor compartment.
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24. • Samples are withdraw through sampling port of the diffusion cell at predetermined
time interval over 24 hr and are analysed.
• The receptor phase is immediately replenished with equal volume of fresh diffusion
buffer.
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25. MARKETED PRODUCT
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Drug Trade Name Type of Devices Indication
Scopolamine Transderm-Scop Reservoir Motion sickness
Nitroglycerine Transderm-Nitro Reservoir Angina
Nitro-Dur Monolithic
Nitrodisc Monolithic
Estradiol Estraderm Reservoir and ethanol
enhancer
Hormone treatment

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Drug Trade name Producer-Marketer
Minocycline Sunstar American Cyanamide, Takeda
Estradiol+Norethister
one
Estracombi TIS Ciba-Geigy, Alza
DHEA Pharmedic
Fentanyl
Triamcinolone
acetonide
Whitby Pharm.

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