Transdermal drug delivery system

1. Presented by;
Alka Diwakar
M.Pharm (Pharmaceutics)
1st Semester (2019-2020)
CSJM UNIVERSITY KANPUR
UNIVERSITY INSTITUTE OF PHARMACY
TRANSDERMAL DRUG
DELIVERY SYSTEM
1CSJM UNIVERSITY KANPUR

2. INTRODUCTION
The passage of substance from the outside of the
skin through its various layers into the bloodstream.
Definition: Transdermal drug delivery system can deliver the
drugs through the skin portal to systemic circulation at a
predetermined rate and maintain clinically the effective
concentration over the prolonged period of time.
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3.  Transdermal drug delivery system (TDDS)also know as
pacth’s are dosage from designed to deliver
therapeutically effective amount of drug across a
patient’s skin
 The primary objective of controlled drug delivery is to
ensure safety and efficacy of the drug as well as
patients compliance.
 TDDS a realistic application as the next generation of
drug delivery.
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4. ANATOMY OF SKIN
 It composed of 3 layer-
a) Epidermis-
i) Stratum Corneum
ii) Stratum Lucidum
iii) Stratum Granulosum
iv) Stratum Spinosum
b)Dermis
c)Subcutaneous
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5. PATHWAY OF DRUG ABSORPTION
THROUGH THE SKIN
 Intercellular diffusion through
lipid layer.
 Transcellular diffusion through
lipid bilayer and keratinocytes .
 Diffusion through hair follicles
and sweat ducts.
The lipophilic drug pass mainly
through the lipid matrix present
in the stratum corneum .
The hydrophilic drug permeate
through hydrated stratum
corneum by polar pathway.
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6. FUNDAMENTALS OF SKIN PERMEATION
Rate of permeation dQ/dt across a skin can be expressed
as
dQ/dt = Ps[ Cd - Cr ]
Where
dQ/dt – Rate of permeation
Ps – Permeability coefficient
Cd – Concentration in donor compartment
Cr – Concentration in receptor compartment
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7. FACTORS AFFECTING
TRANSDERMAL BIOAVAILABILITY
.
 Physiological factors
 Formulation factors
 Physicochemical
factors.
 Physiological factors
1. Hydration of skin
2. Skin temperature
3. Skin age
4. Blood flow
5. Regional skin sites
6. Skin metabolism
Contd…CSJM UNIVERSITY KANPUR 7

8. Formulation factor
 Release rate of the
drug
 Ingredient of the
formulation
Presence of permeation
enhancers
Physicochemical
factors of drug
 PH
 Diffusion coefficient
 Partition coefficient
 Drug concentration
 Molecular size and
shape
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9. Contd...
Advantages of TDDS
 Avoidance of first-pass effect,
 Comparable characteristic with IV infusion.
 Ease of termination of drug action, if necessary.
 Long duration of action.
 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
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10. DISADVANTAGES OF TDDS
 Transdermal drug delivery system cannot deliver ionic drugs.
 It cannot achieve high drug levels in blood.
 It cannot develop for drugs of large molecular size.
 It cannot develop if drug or formulation causes irritation to
skin.
 Possibility of local irritation at site of application.
 May cause allergic reaction.
 Long time adherence is difficult.
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11. TYPES OF TRASDERMAL PATCHS
1. SINGLE-LAYER DRUG-IN-ADHESIVE
2. MULTI-LAYER DRUG-IN-ADHESIVE
3. RESERVOIR SYSTEM
4. MATRIX SYSTEM
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12. SINGLE-LAYER DRUG-IN- ADHESIVE
 The adhesive layer of this system contains the drug.
 The adhesive layer not only severs adhere the various
layer together, along with the entire system of the skin,
but it is also responsible for the releasing of the drug.
 The adhesive layer is surrounded by a temporary liner and
a backing
 Example –Deponit
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13. MULTI-LAYER DRUG-IN-ADHESIVE
 Similar to the single layer system in the both adhesive layer
are also responsible for the releasing of the drug.
 In add another layer of drug-in adhesive usually separated by a
membrane .
 The patch also has a temporary liner layer and permanent
backing .
 Example- Nicotrol.
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14. RESERVOIR SYSTEM
 Reservoir transdermal system has a separate drug layer.
 The drug layer is a liquid compartment containing a drug
solution or suspension separated by the adhesive layer.
 This patch is also packed by the backing layer this type of
system the rate of release is zero oder.
 Example – Transdermal -Nitro
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15. MATRIX SYSTEM
 Matrix system has a drug layer of a semisolid matrix
containing a drug solution or suspension .
 The adhesive layer in this patch surrounded the drug layer
partially over layering it.
 Example – Nitro-Dur.
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16. TYPES OF TRANSDERMAL PATCHES
AVAILABLE TODAY
 Transdermal patch Nicotine.
 Transdermal patch for severe pain.
 Transdermal patch for harmone therapy.
 Transdermal patch for anti hypertensive,
 Transdermal patch for anti depressant.
 Transdermal patch for deficit hyper activity disorder.
 Transdermal patch for vitamin B12.
 Transdermal patch for easy breath.
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17. MARKETED TRANSDERMAL
PATCHS
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18. FORMULATION OF TRANSDERMAL PATCH
COMPONENT EXAMPLES
DRUG Fentanyl, Ketoprofen
Polymer matrix
Synthetic polymers Polyvinyl alcohol, Polypropylene.
Natural polymers Gums, Waxes, Starch.
Penetration enhancers Water, Alcohols, Glycols, Fatty acid
Adhesive Polyisobutylene.
Backing membrane Silicon
Release liner Laminates of metals and foils of polyesters.
Other excipients
Solvent Methanol, Chloroform, Acetone.
plasticizer Propylene glycol .CSJM UNIVERSITY KANPUR 18

19. EVALUATION
In-vivo evaluation
In- vitro
evaluation
Physicochemical
evaluation
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20. Physicochemical Evaluation
 Thickness of patch
 Weight uniformity
 Drug content determination
 Content uniformity
 Folding endurance
 Flatness
 Percentage moisture content
 Interaction studies
 Percentage moisture uptake
 Water vapour permeability
evaluation
 Tensile strength
 Evaluation of adhesive
A. shear adhesion test
B. Peel adhesion test
C. Tack properties
a) Thumb tack test
b) Rolling ball test
c) Quick stick (peel tack test)
test
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21. Physicochemial evaluation
 Interaction studies
Interaction studies(drug and excipient).
Interaction studies ( drug and excipients ) are commonly
carried out in Thermal analysis, Fourier transform infrared
spectroscopy (FTIR), UV and chromatographic techniques by
comparing their physicochemical characters such as assay,
melting point, wave numbers, absorption maxima etc.
 Thickness of the patch:
The thickness of the drug loaded patch is measured in
different points by using a digital micrometer.
.
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22. Cont.
 Weight uniformity:
The prepared patches are to be dried at 60°c for
4 hrs before testing.
Individually weighing 10 randomly selected patches a
specified area of patch is to be cut in different parts of the patch
and weigh in digital balance.
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23. Cont....
 Drug content determination:
accurately weighed portion of film (about 100 mg) is
dissolved in 100 ml of suitable solvent & shaken
continuously for 24 h, then sonicated
After sonication and subsequent filtration, drug in
solution is estimated spectrophotometrically
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24. Cont..
 Content uniformity test:
10 patches are selected, in 9 out of 10 patches have content
between 85% to 115% and 1 has content not less than 75% to
125% of the specified value, patches pass the test
3 patches range of 75% to 125%, then additional 20 patches are
tested . If these 20 patches have range from 85% to 115%, then
the transdermal patches pass the test.
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25. Cont...
 Folding endurance:
 Flatness test:
In flatness determination one strip is cut from the centre and two
from each side of patches. The length of each strip is measured
and variation in length is measured by determining percent
constriction. 0 % constriction is equivalent to 100 % flatness.
% constriction = I1 – I2 X 100 ∕I1
I1 = Initial length of each strip I2 = Final length of each strip
Repeatedly folding a small strip of the patch at the
same place till it broke. The number of times the
patch could be folded at the same place without
breaking Folding endurance value
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26. Cont....
 Percentage Moisture content:
 calcium chloride
 Percentage moisture content = [Initial weight - Final
weight/ Final weight] ×100
 Percentage Moisture uptake:
 potassium chloride
 Percentage moisture uptake = [Final weight - Initial
weight/ initial weight] ×100
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27. Cont...
 Evaluation of adhesive
a) Shear Adhesion test:
Shear adhesion strength is determined by measuring (cohesive
strength of an adhesive polymer) the time it takes to pull the
tape off the plate.
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28. Cont....
b) Peel Adhesion test:
 In this test, the force required to remove an adhesive coating
form a test substrate is referred to as peel adhesion.
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29. cont
c) Tack properties:
 It is ability of a polymer to adhere to a substrate with little
contact pressure. Test is includes.
 Thumb tack test:
 It is a qualitative test and the force required to remove thumb
from adhesive is a measure of tack.
 Rolling ball tack test:
 In this test, stainless steel ball of 7/16 inches in diameter is
released on an inclined track so that it rolls down and comes
into contact with horizontal, upward facing adhesive.
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30. Cont....
 Quick Stick (peel-tack) test:
 The peel force required breaking the bond between an
adhesive and substrate is measured by pulling the tape away
from the substrate at 90 at the speed of 12 inch/min.
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31. Cont.....
 Probe Tack test:
 The tip of a clean probe is contact with adhesive and bond is
formed between probe and adhesive.
 The force required to pull the probe away from the adhesive
at fixed rate is recorded as tack and it is expressed in grams
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32. In- vitro evaluation
In-vitro drug release
studies
In-vitro skin
permeation studies
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33. In-vitro evaluation
 In- vitro drug release studies
 A number of mathematical model is describe the drug
dissolution kinetics from controlled release drug delivery
system e.g., Higuchi model, First order, Zero order and Peppas
& Korsenmeyer model.
 The dissolution data is fitted to these models and obtained
the release mechanism of the drug. There are various
methods available for determination of drug release rate of
TDDS.
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34. Cont..
 Higuchi model
A=[D (2C-Cs) Cs x t] ½
A – amount of drug released
in time ‘t’ per unit area
C – initial drug concentration
Cs – drug solubility in the
matrix media
D – diffusivity of drug
molecule in the matrix
substance
 Peppas & Korsenmeyer
model
F = (Mt/M) = Km tn
F – fraction of drug release at
time ‘t’
Mt - amount of drug release at
time ‘t’
M – total amount of drug in
dosage form
Km - kinetic constant
n – diffusion or release
exponent
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35. cont.
 Paddle over disc: (USP apparatus 5)
 This method the transdermal system is attached to a disc or
cell resting at the bottom of the vessel which contains medium
at 32 ±5°C.
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36. Cont...
 Cylinder modified USP Basket: (USP apparatus 6)
This method is similar to the USP basket type dissolution
apparatus, except that the system is attached to the surface of a
hollow cylinder immersed in medium at 32 ±5°C.
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37. In – vivo evaluation
1. Animal models:
 In-vivo animals models are preferred because considerable
time and resources are required to carry out studies in humans.
Some of the species are used : mouse, rabbit, rat, cat, dog, pig,
house, monkey small hairy animals (e.g. rat, rabbit) is most
reliable or in vivo evaluation of transdermal patches standard
radiotracer methodology used.
2. Human models:
 It is first described by Fieldman and Maibach.
 They includes determination of percutaneous absorption by an
indirect method of measuring radioactivity in excreta following
topical application of the labeled drug. 14C is generally used
for radio labeling.
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38. Cont....
(a) Reservoir technique :
It makes use of the relationship
between stratum corneum
reservoir function and in vivo
percutaneous absorption to
predict in vivo penetration.
This method is involves a
simple, short exposure of the
skin to the compound under
study followed by removal of
the stratum corneum by tape
stripping and analysis of the
content of the compound in
the stratum corneum.
(b) Mass balance technique
The application site is covered
with an occlusive chamber,
the chamber being replaced by
a new one after a particular
time interval. The site is also
subjected to washing at these
time.
Radio labeling techniques are
used and the chamber,
washing and the faces and
urine of the patients are
subjected to analysis. In this
technique include
achievement of mass balance
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39. ADVANCES IN TRANSDERMAL DRUG
DELIVERY SYSTEMS
 Transdermal drug delivery technologies are becoming one
of the fastest growing sectors with in the pharmaceutical
industry.
 Advance in drug delivery systems having increasingly
brought about rate controlled delivery with fewer side
effects as well as increased efficacy and constant drug
delivery.
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40. REFERENCES
1. Y.W. Chien, Noval Drug Delivery Systems, 2nd edition,
revised and expanded, Marcel Dekker, Inc., new York,
1992.
2. N. K. Jain, Controlled and Noval Drug Delivery ,CBS
Publishers & Distributors, New Delhi, first edition 1997
3. (reprint in 2001). Jain NK. Controlled And Novel Drug
Delivery. 1st edition. CBS Publishers &
Distributors.1997,107-110.
4. Rolling ball tack test for adhesive evaluation T Himanshi,
S Ruchika. Transdermal Drug Delivery System: A Review.
International Journal Of Pharmaceutical Sciences And
Research. 2016;7(6): 2274-90
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