Transdermal Drug Delivery systems as per IV B.Pharm NDDS

1. TRANSDERMAL DRUG DELIVERY
SYSTEMS
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Dr. Raghavendra Kumar Gunda
Assistant Professor,
Department of Pharmaceutical Sciences, Vignan’s Deemed to be University
Vadlamudi, Andhra Pradesh

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.

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.

5. DISADVANTAGES
▫ Drug that require high blood levels
administered or if drug dose required for
cannot be
therapeutic
transdermal
value is more than 10-25 mg/day, the
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.
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6. DISADVANTAGES
• 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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7. 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

8. 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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9. B. DERMIS
which contain blood vessels, lymphatic & nerve endings,
there by providing physiological support forepidermis.The
dermis is the layer of tissue that is Deeper and Thicker than
epidermis.
• It is also called as Hypodermis.
• It is made up of loose connective tissue, including
Adipose tissue.
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It is composed of network of collagen & elastic fibers
embedded in a mucopolysaccharide matrix,
C. SUBCUTANEOUS TISSUE

10. Pathways of drug penetration
1 Transcellular route
2 Intercellular route
3 Transappendageal route
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11. PERMEATION OF DRUG MOLECULE THROUGH SKIN
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• Mechanism involved is Passive Diffusion .
• This can be expressed by Fick’s First law of Diffusion-
dq/dt = D KA( 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

12. A. SKIN CONDITION
• Thickness of stratum corneum
• Presence of hair follicle
• Trauma
• Hydration of skin
• Age
B. EXTERNALFACTORS
• Environmental humidity and
temperature
• Exposure to chemicals
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FACTORS THAT INFLUENCE TRANSDERMAL
DRUG DELIVERY

13. DESIGN OF TRANSDERMALSYSTEM
The main components to a transdermal patch are:
• Liner - Protects the patch during storage. The liner is
removed prior to use.
• Drug - Drug solution in direct contact with release liner
• Adhesive - Serves to adhere the components of the patch
together along with adhering the patch to the skin

14. DESIGN OF TRANSDERMALSYSTEM
• Membrane - Controls the release of the drug from the
reservoir and multi-layer patches
• Backing - Protects the patch from the outer environment
• Permeation Enhancer - These are permeation
promoters for drugs, which increases delivery of drug.

15. Components of transdermal patch
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16. 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
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17. B. PHYSICAL STIMULI ACTIVATED SYSTEM
• It mainly include –
1. Iontophoresis
2. Electroporation
3. Sonophoresis

18. 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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20. B. Matrix Type
• It is formed by homogenously dispersing the drug in
a mixture ofhydrophilic–Lipophilic polymer{matrix}
and the medicated polymer is moulded on the
medicated disc of defined surface area and thickness .
• It is then glued over an occlusive base plate consisted
of compartment fabricated using an impermeable
plastic backing.

22. C. AdhesiveType
• It is prepared by directly dispensing the drug in
an adhesive polymer and 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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24. D. Microreservoir Type
• It has features of both reservoir and 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 drugsuspension is dispersed homogenously in a
Lipophilic polymer, by high shear mechanical agitation
to form thousands of microspheres of drug.

26. 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
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27. EVALUATION PARAMETERS
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.
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29. 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.
1 No Erythema 2. Slight Erythema (light pink)
3. Moderate Erythema (dark pink) 4. Moderate to severe Erythema (light
red) 5. Severe Erythema (extreme redness)

30. 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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31. 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 donorcompartment.
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32. • 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.

33. 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

34. Drug Trade name Producer-Marketer
Minocycline Sunstar American Cyanamide,
Takeda
Estradiol+Nor
ethister one
Estracombi
TIS
Ciba-Geigy, Alza
DHEA Pharmedic
Fentanyl
Triamcinolone
acetonide
Whitby Pharm.

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