1)Introduction 2)Advantages and Disadvantages 3)Structure of Skin 4)Permeation through skin 5)Factors affecting permeation 6)Basic Componentes of TDDS 7)Formulation approaches used in the development of TDDS 8)Evaluation of TDDS 9)Reference

1. Transdermal drug delivery System
Presented By:
Miss. Shubhangi Parbhane
First Year M. Pharm
(Dept. of Pharmaceutics)
Sub: Drug Delivery System
Alard Collage of Pharmacy, Marunji
Under the Guidance of:
Dr. Nalanda Borkar
HOD ( Pharmaceutics)
Alard Collage of Pharmacy, Marunji
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2. Contents
Introduction.
Advantages & Disadvantages
Structure of the skin.
Permeation through skin.
Factors affecting permeation.
Basic components of TDDS
Formulation approaches used in the development of TDDS
Evaluation of TDDS
References.
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3. INTRODUCTION:
Definition:
Transdermal therapeutic systems are defined as self contained ,self discrete dosage
forms ,which when applied to the intact skin deliver the drug at a controlled rate to the
systemic circulation.
A simple patch that you stick onto your skin like an adhesive bandage, which utilize
passive diffusion of drugs across the skin as the delivery mechanism.
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4. ADVANTAGES
Avoidance of first-pass effect
Long duration of action
 Comparable characteristics with IV infusion
 Ease of termination of drug action, if necessary
No interference with gastric and intestinal fluids
Suitable for administered of drug having- Very short half-life, e.g.
nitroglycerine. Narrow therapeutic window.
Poor oral availability.
DISADVANTAGES
Poor diffusion of large molecules
 Skin irritation
 Requires high drug load
Unsuitable –If drug dose is large
 Absorption efficiency is vary with different sites of skin.
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5. Structure of the skin
 Anatomically the skin has many
histological layers, but it is divided into
three layers .
 Epidermis .
 Dermis .
 Subcutaneous tissue.
 Epidermis
 The epidermis is divided into
following parts The stratum corneum and
stratum germinativum.
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6. The stratum corneum forms the outer most layer of the epidermis and consists
many layers of compacted , flattened, dehydrated keratinized cells in the stratified
layer.
The stratum corneum is responsible for the barrier function of the skin and
behaves as a primary barrier to the percutaneous absorption.
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.
Below the dermis there is a fat containing subcutaneous tissue .
Upper portion of the dermis is formed into ridges containing lymphatics and nerve
endings.
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7. Subcutaneous
This is a sheet of the fat containing areolar tissue known as the superficial fascia.
attaching the dermis to the underlying structures .
PERMEATION OF DRUG MOLECULE THROUGH SKIN
It express by Fick’s first law of Diffusion-Drug molecule diffuse from a region of
higher conc. to one of lower conc. until equilibrium is attained.
Fick’s First law of Diffusion
dm/dt = J = D A K/h
Where,
dm / dt =J= study state flux,
D = diffusion
A = surface area,
K = partial coefficient between the Stratum corneum and the vehicle,
h = diffusional path length or membrane thickness
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8. Subcutaneous
This is a sheet of the fat containing areolar tissue known as the superficial fascia.
attaching the dermis to the underlying structures
Permeation through skin.
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9. Permeation through skin.
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10. Factors influencing dermal penetration of drugs
I. Biological factors:
1. Skin condition
2. Skin age
3. Blood flow
4. Regional skin site
5. Skin metabolism
6. Species difference.
II. Physicochemical factors:
1. Skin hydration
2. Temperature and pH
3. Diffusion coefficient
4. Drug concentration
5. Partition coefficient
6. Molecular size and shape.
7. Solubility, ionization.
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11. Increase in Conc. of drug in vehicle increases amount of drug absorbed per unit of
surface area per time interval.
The drug in vehicle must interface the skin surface in sufficient conc.
 More drug is absorbed when it is applied to large surface area.
 Drug should have greater physicochemical attraction to the skin than to dispersed
vehicle.
 The aqueous solubility of drug determines the conc. present at the absorption
site.
 The partition coefficient influences the rate of transport across the absorption
site.
Hydration of the skin softens stratum cornium, increases the size of pores,
allowing greater flow of substances. Site of application influences degree of drug
absortion. Skin in post auricular layer is more permeable to drugs.
Longer the contact period of drug with skin, greater will be absorption.
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12. Basic components of transdermal drug delivery systems The components of
transdermal devices include :
1. Polymer matrix or matrices
2. The drug
3. Permeation enhancers
4. Other Excipients –
a) Adhesives
b) Backing membrane
c) Protective liner
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13.  Polymer matrix :
The polymer controls the release of drug from the device.
The following criteria should be satisfied for a polymer to be used in a transdermal
system : Molecular weight, glass transition temperature & chemical functionality of the
polymer should be such that the specific drug diffuses properly & gets released through
it.
 The polymer should be stable, non reactive with the drug.
Easily manufactured & fabricated into the desired product & must be inexpensive.
The polymer & its degradation products must be non toxic or non antagonistic to the
host.
The mechanical properties of the polymer should not deteriorate excessively when
large amounts of active agent are incorporated into it.
 Nature of origin as : Natural polymers Cellulose derivatives, Zein, Gelatin, Shellac,
Waxes, Proteins, Gums & their derivatives, natural Rubber, Starch .
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14. Synthetic elastomers
Hydrin rubber, Polysiloxane, Silicone rubber, Nitrile, Acrylonitrile, Butyl rubber,
Styrene – butadiene rubber, Neoprene etc.
Synthetic polymers :Polyvinyl alcohol, Polyvinyl chloride, Polyethylene,
Polypropylene, Polyacrylate, Polyamide, Polyurea, PVP, Polymethylmethacrylate,
Epoxy, EVA, Polyisobutylene.
 The drug :
Following are some of the desirable properties of a drug for transdermal delivery :
Physicochemical properties
a.The drug should have a molecular weight less than approximately 1000 daltons.
b. The drug should have a balanced hydrophilic & lipophilic nature. Extreme
partitioning characteristics are not conducive to successful drug delivery via skin.
c. Should have a low melting point.
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15.  Biological properties
 The drug should be potent with a daily dose of the order of a few mg/day.
 The half life (t1/2) of the drug should be short.
 The drug must not induce a cutaneous irritant or allergic response.
 Suitable candidates for transdermal delivery may be drugs, that –
•Degrade in the GI tract e.g – Nitroglycerine
•Inactivated by hepatic first pass effect e.g - β blockers, Ca2+ channel blockers etc.
• Which have low bioavailability e.g – Nicorandil
• Which cause severe local side effects when administered orally e.g. Tenoxicam.
•Transdermal patches are usually suitable for chronic therapy. e.g. – hypertension,
diabetes, angina pectoris etc.,
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16. Penetration Enhancers :
Desirable properties for penetration enhancers :
 They should be non-toxic, non-irritating and non allergenic.
They would ideally work rapidly, and the activity and duration of effect should be
both predictable and reproducible.
They should have no pharmacological activity within the body— i.e. should not
bind to receptor sites.
The penetration enhancers should work unidirectionally, i.e. should allow
therapeutic agents into the body whilst preventing the loss of endogenous material
from the body.
When removed from the skin, barrier properties should return both rapidly and fully.
Should be appropriate for transdermal formulation i.e. compatible with both
excipients & drugs.
They should be cosmetically acceptable with an appropriate skin ‘feel’.
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17.  Classification of Permeation enhancers:
a. Solvents
b. Surfactants
i) Anionic surfactants: Dioctyl sulphosuccinate, Sodium lauryl sulphate.
ii) Non-ionic surfactants: Pluronic F127, Pluronic F68
iii) Bile salts : Sodium taurocholate,Sodium deoxycholate.
c. Binary systems : Propylene glycol, oleic acid
d. Miscellaneous chemicals : Urea, Calcium thioglycholate.
Other excipients
•Adhesives –The fastening of the transdermal device is usually done by the adhesive .
The adhesive should satisfy the following criteria .
Do not irritate or sensitize the skin.
Adhere to the skin during the dosing interval.
It should be easily removed .
 It should not leave any unwashable residue.
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18. Backing membrane
They are flexible and provide a good bond to the drug reservoir , prevent the drug
from leaving the dosage form through top.
It is an impermeable membrane that protects the product during the use on the skin.
Contains formulation throughout shelf-life and during wear period
Must be compatible with formulation (nonadsorptive)
Printable ,g: metallic plastic laminate , plastic backing with adsorbent pad adhesive
foam pad .
Liner :
It protects the patch during storage.
The liner is removed prior to use.
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19. Type of Transdermal Patches
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20. How To Designs Transdermal Patch:
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21. Evaluation of TDDS
1. Physical evaluation:
a) Film thickness,
b) % Flatness,
c) Folding endurance,
d) Tensile strength/ shear strength.
2. Weight variation
3. Drug content
4. % Moisture content
5. % Moisture uptake
6.Adhesive evaluation:
a. Peel adhesion test,
b. Tack properties (thumb tack test, rolling ball tack test, quick- stick/ peel- tack test,
probe tack test)
7. In-vitro drug release evaluation/ skin permeation studies.
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22. 1.Physical evaluation
a. Film thickness: Electronic verniercalipers – 5 different points of patch ---- Average
thickness.
b. % Flatness: Cut 3 strips of 7cm form film (2 from corners + 1 center) – length
measured with out applying pressure --- % Flatness = average % length.
c. Folding endurance: Repeatedly folding small strip of film (2x2 cm) at the same
place until it beaks. Count no. of time the film is fold.
d. Tensile strength/ Shear strength: Modified pulley system --- measure force required
to break the system (Kg/ cm2)
2. Weight variation:
Weigh 10 randomly selected patches,
calculate average weight and % Weight variation.
3. Drug content: Take 5cm2 film, cut to pieces + 100ml Phosphate buffer (pH 7.4) ----
shake 24 hrs ---- ultra-sonictaed 15 min ----- filter -- - measure absorbance
spectrophotometrically.
4. % moisture content: Initial weight of film (W1) ---- store in desiccator with
activated silica, room temp, 24 hrs. ------ repeatedly weigh film until constant weight
(W2).
5. % moisture uptake: Keep film in desiccator, 24 hrs ---- initial weight of film (W1) --
- expose to 85% RH (Saturated aluminum chloride solution) ---- repeatedly weigh film
until constant weight (W2).
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23. 6.Adhesive evaluation:
1.Peel adhesion test:
• Peel adhesion is the force required to remove an adhesive coating from a test
substrate is referred to as peel adhesion.
• Peel adhesion properties are affected by molecular weight of adhesive, amount of
additives & polymer composition.
• It is tested by measuring the force required to pull a single coated tape applied to a
substrate, at a 180o angle.
• If higher value then it indicates greater bond strength.
2. Tack properties:
• Tack is the ability of a polymer to adher to a substrate with little contact pressure.
Tack depends on mol. wt. and composition (tackifying resins) of polymer
I. Probe tack test
A. Thumb tack test: Evaluation is done by briefly pressing the thumb on to adhesive.
B. Rolling ball tack test: Measurement of distance that a stainless steel ball travels
along upward facing adhesive. If adhesive is less tacky, ball travels more distance.
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24. C. Quick- stick/ peel- tack test: Peel force required to break the bond between an
adhesive and substrate is measured by pulling the tape away from the substrate at
900 at a speed 12 inch/min. Force is expressed in ounces (or) grams/inch width.
D. Probe tack test: Force required to pull a probe away form an adhesive at a fixed rate
is recorded as tack in grams.
7. In-vitro drug release evaluation / skin permeation studies.
In-vitro skin permeation can be studied using 1.
a) Franz-diffusion cell
b) Keshary-Chien (K-C) cell.
c) Valia-Chien (V-C) cell,
d)Ghanna m-Chien (G-C) membrane permeation cell,
e) Jhawer-Lord (J-L) rotating disc cell.
Dissolution apparatus:
1. Type-V --- Paddle over disc
2. Type-VI --- Cylinder
3. Type-VII --- Reciprocating holder
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25. Franz-diffusion cell:
• This has a effective permeation area of 1 cm2 and receptor cell volume of 10ml.
• A bar magnet is used for stirring solution in receptor compartment.
Procedure: (Franz-diffusion cell)
1. The receptor compartment is filled with 10 ml of PBS, stirred at 100 rpm and
temp. of 32 ± 1oC is maintained.
2. The skin is carefully checked through magnifying glass to ensure any holes,
surface irregularity.
3. The skin is mounted on receptor compartment with stratum corneum side facing up
in to the donor compartment.
4 . The transdermal system is applied on the skin.
5. samples are withdrawn at regular time intervals through sampling port for 24 hrs
and analyzed.
6. The receptor phase is immediately replenished with equal volumes of fresh
diffusion buffer.
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26. REFERENCE:
1)https://www.slideshare.net/DanishKurien/transdermal-drug-delivery-system-
13541191 / Assessed Date: 4 March 2021
2)https://www.slideshare.net/ArshadKhan63/transdermal-drug-delivery-system-
119177012 / Assessed Date: 4 March 2021
3)https://www.slideshare.net/RahulShirode2/tdds-by-rahul-shirode / Assesed Date: 4
March 2021
4)https://www.slideshare.net/vilegavekailash/transdermal-drug-delivery-system-
222447554 / Assessed Date:5 March 2021
5)https://www.slideshare.net/binujass1/transdermal-drug-delivery-system-149052116
/Assessed Date:5 March 2021
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27. Thank You
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