A brief information on transdermal drug delivery system.

1. SEMINAR ON TRANSDERMAL DRUG
DELIVERY SYSTEM
PREPARED BY: PRIYANKA MANOJ GALHOTRA
(SEM III)
GUIDED BY: MR. V.R. MAHAJAN
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2. INTRODUCTION
• The use of the transdermal route has been well established
since the 1800s. There is considerable interest in the skin as a
site of drug application both for local and systemic effects.
• Transdermal drug delivery system allows delivery of a drug
into the systemic circulation via permeation through skin
layers at a controlled rate.
• The skin poses an extremely good barrier to drug penetration
and it is usually necessary to employ enhancement strategies.
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3. OBJECTIVES
• To explore skin as site for drug administration.
• To identify physicochemical properties of drug
required in development of transdermal drug delivery
system.
• To study various methods for preparation of
transdermal drug delivery system.
• To study various methods for evaluation of
transdermal drug delivery system.
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4. ADVANTAGES
• Avoidance of the first-pass effects.
• Avoidance of significance presystemic metabolism
and therefore need lower doses.
• Can provide adequate absorption of certain drugs
• Avoids the risk and inconvenience of parenteral
therapy
• Drugs inputs can be promptly interrupted simply by
removal of the patch when toxicity occurs.
• Provides suitability of self medication.
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5. ADVANTAGES OF TDDS IN COMPARISON TO
ORALAND INTRAVENOUS FORMULATION
ADVANTAGES INTRAVENOUS ORAL TDDS
Reduced first
pass effects
YES NO YES
Self
administration
NO YES YES
Unrestricted
patient activity
NO YES YES
Non- invasive NO YES YES
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6. DISADVANTAGES
• Adhesive may not adhere well to all types of skin
• Uncomfortable to wear
• May not be economical
• The molecular size of the drug should be reasonable
that it should be absorbed percutaneously.
• Drugs that requires high blood levels cannot be
administered limited only to potent molecules those
requiring a daily dose of 10 mg or less.
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7. PERCUTANEOUS ABSORPTION
• Percutaneous absorption is defined as penetration of
substances into various layer of skin and permeation
across the skin into systemic circulation.
• The percutaneous absorption is a step-wise process and
can be divided into three parts:
• Penetration: Is the entry of substances into a particular
layer.
• Permeation: Is the penetration from one layer into another
and is different both functionally and structurally from the
first layer.
• Absorption: Is the uptake of a substances into systemic
circulation.
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8. Fig: Anatomy of skin along with routes of
penetration
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9. IDEAL PROPERTIES OF DRUGS USED IN
TRANSDERMAL DRUG DELIVERY SYSTEM
PARAMETERS PROPERTIES
Dose Should be low (> 20 mg/day)
Half life in ‘h’ 10 or less
Molecular weight < 400
Partition coefficient Log P (octanol-water) between 1-4
Skin permeability coefficient > 0.5X10¯³ cm/hr
Skin reaction Non- irritating and non -sensitizing
Oral bioavailability Low
Therapeutic index Low
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10. APPROACHES OF TRANSDERMAL DRUG
DELIVERY SYSTEM
• Various technologies have been developed to bypass or
modulate the barrier function of the skin and to allow
easier passage of drugs into the dermal microcirculation,
these can be categorized into physical and chemical
• PHYSICALAPPROACHES: Ionotophoresis,
Electroporation, Microporation, Heat, Needless
injections, Medicated tattoo, Sonophoresis, Pressure
valve, Ratio frequency, Magnetophoresis.
• CHEMICALAPPROACHES: Prodrug approaches,
penetration enhancer.
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11. PHYSICALAPPROACHES
• IONTOPHORESIS: Is the process of enhancing the
permeation of topically applied therapeutic agents.
• The drugs is applied under an electrode of the same charge as
the drug and an indifferent counter electrode is positioned
elsewhere on the body.
• The active electrode effectively repels the active substances
and forces it into the skin and rough the skin by the application
of electric current.
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12. 12

13. ELECTROPORATION
• Is another electrical enhancement method which
involves the application of short (microsecond or
millisecond ), high voltage (50-1000 volts) pulses to
the skin.
• Larger macromolecules have also been delivered by
electroporation, including insulin, vaccines,
oligonucleotides and microparticles.
• A few model compounds drugs have also been
studied for increased transdermal absorption by
electroporation.
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14. SONOPHORESIS
• Is a techniques which involves the use of ultrasonic
energy to enhance skin penetration of active
substances.
• Transdermal enhancement is particularly significant
at low frequency regims (20 KHz < f < 100 KHz)
than when induced by high frequency ultrasound.
• Ultrasound parameters such as treatment duration
intensity, pulse length and frequency are all known to
affect percutaneous absorption with frequency being
the most important.
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15. CHEMICALAPPROACHES
• PENETRATION ENHANCER: Incorporation of
penetration enhancer facilitates the absorption of
drugs by altering the barrier property of the stratum
corneum.
• A permeation enhancer should be pharmacologically
inert, non-toxic, non-irritating, non-allergic, odorless,
tasteless, colorless, compatible with most drugs and
excipients, inexpensive and have good solvent
properties.
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16. DIFFERENT CLASSES OF PENETRATION
ENHANCERS
CLASSES EXAMPLES
Alcohols and polyols Ethanol, propylene glycol
Surfactants Tween, span, SLS
Fatty acids Oleic acid
Amines and amide Azone, N-methyl
pyrrolidone
Terpenes Limonene
Sulfoxide Dimethylsulfoxide
Esters Isopropylmyristate
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17. PRODRUGS
• Prodrugs are therapeutically inactive derivatives of
therapeutically active drugs.
• A prodrug undergoes metabolism to produce the
therapeutically active drugs.
• A prodrug is more lipophilic than the parents drugs
and has different physicochemical properties
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18. FORMULATION ASPECTS
• Basic components of Transdermal drug delivery
system:
• Polymer matrix
• Drug
• Permeation enhancers
• Adhesive layers
• Backing layer
• Release liner
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19. POLYMERS MATRIX
• Advances in transdermal drug delivery technology
have been rapid because of the sophistication of
polymer science that allows incorporation of
polymers in transdermal system in adequate quantity.
• Selection of polymeric membrane is very important
in designing a variety of membrane permeation
controlled transdermal drug delivery system.
• Examples: Gelatin, Sodium alginate, Gum tragacanth,
methyl and ethyl cellulose, HPMC
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20. DRUGS
• For successfully developing the transdermal drug delivery
system, the drug should be chosen with great care. The
following are some of the desirable properties of drugs
for transdermal drug delivery.
PHYSICOCHEMICAL PROPERTIES BIOLOGICAL PROPERTIES
Drug should have a molecular weight
less than app 1000 daltons
The drug should be potent with a daily
dose of the order of a few mg/day
The drug should have affinity for both
lipophilic and hydrophilic phases.
The half life t1/2 of the drug should be
short
Drug should have a low melting point
usually below 200°C
The drug should be non-irritating and
non-allergic
Skin has pH of 4.2 to 5.6, solutions
which have pH are used to avoid
damage the skin
Drugs which degrade in the gastro
intestinal tract or inactivated by hepatic
first pass effect are suitable candidates
for transdermal effects 20

21. PERMEATION ENHANCERS
• These are the compounds which promotes skin
permeability by altering the skin as a barrier to the
flux of a desired penetrant.
D = Diffusion coefficient
c= the concentration of the membrane resistance
x=the spatial coordinate
J= D X dc
dx
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22. ADHESIVE LAYER
• The adhesive must posses sufficient properly so as to
firmly secure the system to the skin surface and to
maintain it in position for as long as desired, even in the
presence of water.
• Adhesion is understood to be the net effect of three
phenomenon’s namely;
• Peel : The resistance against the breakage of adhesive
bond
• Track: The ability of a polymer to adhere to a substrate
with little contact pressure
• Creep: The viscous relaxation of the adhesive bond upon
shear.
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23. BACKING LAYER
• The backing layer must be impermeable to drug and
permeation enhancers.
• The backing membranes serves the purposes of
holding the entire system together and at the same
time protects the drug reservoir from exposure to the
atmosphere, which could results in the breakage or
loss of the drug by volatilization.
• Examples: Polyester, aluminized polyethylene
terapthalate, siliconised polyethylene
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24. RELEASE LINER
• The peel strip prevents the loss of the drug that has
migrated into the adhesive layer during storage and
protects the finished device against contamination.
• Examples: Polyesters foils and other metalized
laminates.
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25. METHODS OF TRANSDERMAL DRUG
DELIVERY SYSTEMS
• Asymmetric TPX membrane method
• Circular teflon mould method
• Mercury substrate method
• By using IPM membranes method
• By using EVAC membranes method
• Aluminium backed adhesive film method
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26. EVALUATION OF TRANSDERMAL DRUG
DELIVERY SYSTEM
• Thickness of the patch
• Weight uniformity
• Folding endurance
• Percentage Moisture content
• Percentage Moisture uptake
• Drug content
• Water vapour permeability (WVP) evaluation
• Uniformity of dosage unit test
• Shear Adhesion test
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27. • In vitro drug release studies
• In vitro skin permeation studies
• Skin irritation study
• Stability studies
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28. 1. THICKNESS OF THE PATCH:
The thickness of the drug loaded patch is measured in different
points by using a digital micrometer and determines the average
thickness and standard deviation for the same to ensure the
thickness of the prepared patch.
2. WEIGHT UNIFORMITY:
The prepared patches are to be dried at 60°C for 4hrs before
testing.
A specified area of patch is to be cut in different parts of the patch
and weight in digital balance
The average weight and standard deviation values are to be
calculated from the individual weights.
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29. 3. FOLDING ENDURANCE:
A strip of specific are 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 folding endurance.
4. PERCENTAGE MOISTURE CONTENT:
The prepared films are to be weighed individually and to be kept in a
desiccator containing fused calcium chloride at room temperature for
24 hrs.
After 24 hrs the films are to be reweighted and determine the
percentage moisture content from the below mentioned formula.
% moisture content=[Initial weight – Final weight / Final weight] X
100
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30. 5. PERCENTAGE MOISTURE UPTAKE:
The weighted films are to kept in a desiccator at room
temperature for 24 hrs containing saturated solution of potassium
chloride in order to maintain 84% RH.
After 24 hrs the films are to be reweighed and determine the
percentage moisture uptake from the below mentioned formula.
% moisture uptake= [Final weight-Initial weight/initial
weight] X 100.
6. DRUG CONTENT:
A specified area of patch is to be dissolved in a suitable solvent in
specific volume.
The solution is to be filtered through a filter medium and analyse
the drug contain with the suitable method.
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31. 7. UNIFORMITY OF DOSAGE UNIT TEST:
An accurately weighted portion of the patch is to be cut into small
pieces and transferred to a specific volumetric flask, dissolved in a
suitable solvent and sonicate for complete extraction of drug from
the patch and made up to the mark with same.
The resulting solution was allowed to settle for about an hour and
the supernatant was suitably diluted to give the desired
concentration with suitable solvent.
The solution was filtered using o.2m membrane filter and analysed
by suitable analytical technique and the drug content per piece will
be calculated.
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32. 8. SHEAR ADHESION TEST:
An adhesive coated tape is applied onto a stainless steel plate; a
specified weight is hung from the tape, to affect it pulling in a
direction parallel to the plate.
Shear adhesion strength is determined by measuring the time it
takes to pull the tape off the plate. The longer the time take for
removal greater is the shear strength.
9. SKIN IRRITATION STUDY:
Skin irritation and sensitization testing can be performed on
healthy rabbits (average weight 1.2 to 1.5 kg).
The dorsal surface (50cm²) of the rabbit is to be cleaned and
removed the hair from the dorsal surface and apply the
formulation. The patch should be removed after 24 hrs.
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33. 10. IN VITRO DRUG RELEASE STUDIES:
The paddle over disc method (USP apparatus V) can be
employed for assessment 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
plate and operated at a speed of 50 rpm. Sample can be
withdrawn at app time intervals up to 24 hrs and analyzed
by UV spectroscopy.
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34. 11. IN VITRO SKIN PERMEATION STUDIES:
The study is carried out by using diffusion cell.
The male Wistar rats skin weighing 200-250g used.
Skin is equilibrated for an hour in dissolution medium or
phosphate buffer (7.4) before starting the experiment and placed
in the magnetic stirrer. Temperature was maintained at 32 0.5C.
The isolated rat skin piece is to be mounted between the
compartments of the diffusion cell, with the epidermis facing
upward into the donor compartment.
Sample volume to be removed from receptor compartment at an
regular interval and equal volume of fresh medium is to be
introduced.
Samples analyzed using the UV spectroscopy.
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35. 35

36. 11. STABILITY STUDIES:
Stability studies are to be conducted according to the ICH
guidelines by storing the TDDS samples at 40 0.5 c and 75 5%
RH for 6 months.
The samples were withdrawn at 0, 30 , 60, 90 and 180 days and
analyzed suitably for the drug content.
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37. DRUG BRAND NAME MANUFACTURER
Nicotine Nicoderm GSK
Nicotine Habitraol Novartis
Nitroglycerine Transderm nitro Novartis
Insulin Sono Derm Imarx
Diclofenac diethyl
amine
NuPatch 100 Zudus Cadilla
MARKETED PRODUCT
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38. CONCLUSION
• Due to recent advances in technology and the
incorporation of the drug to the site of action without
rupturing the skin, membrane transdermal route is
effective.
• TDDS has been designed as an alternative, safest, and
easy route for systemic drug delivery system.
• Used as safe and effective drug delivery since 1981.
• Due to advantages this system interest a lot of
researchers.
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39. REFERENCES
• Controlled and Novel Drug Delivery, N.K.Jain.
pp:100-129
• Vyas SP, Khar RK. Targeted and controlled drug
delivery novel carrier system. 1st ed. CBS publishers
and distributors New Delhi; 2002;
pp:411-447
• Lachman, Lieberman’s, The theory and practice of
industrial pharmacy, Fourth edition, CBS publishers
and distributors, pp: 200-203
• Dr. D. Baviskar., Dr. D. Jain Novel Drug Delivery
Systems, Nirali prakashan, pp: 6.1-6.36
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40. THANK YOU
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