1. SHRI RAM MURTI SMARAK COLLEGE OF
ENGINEERING AND TECHNOLOGY OF
BAREILLY
GUIDED BY :
Dr . JITENDRA SINGH
YADAV
PROFESSOR
SRMS CET BLY
PRESENTED BY :
KAUSHIKI SINGH
M.PHARM 1ST YEAR
SRMS CET BLY
GENERAL INTRODUCTION :- TRANSDERMAL DRUG DELIVERY
SYSTEMS..
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2. CONTENTS
• INTRODUCTION.
• STRUCTURE OF THE SKIN.
• ADVANTAGES & DISADVANTAGES.
• MECHANISM OF ABSORPTION THROUGH SKIN.
• PERMEATION ENHANCERS.
• FACTOR AFFECTING PERMEATION.
• BASIC COMPONENTS OF TDDS.
• FORMULATION APPROACHES USED IN THE
DEVELOPMENTS OF TDDS.
• REFERENCES.
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3. INTRODUCTION
• Transdermal drug delivery systems(TDDS) is the
administration of therapeutic agents through the
intact skin for systemic effects.
OR
• TDDS are topically administered medicaments in the
form of patches that deliver drugs for systemic
effects at a pre-determine & controlling rate.
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4. STRUCTURE OF SKIN
• The skin is largest organ of the body.
• The skin surface area 1.8m2 .
FUNCTION OF SKIN
• Protection.
• Regulation of body temperature.
• Formation of vitamin D.
• Absorption & Excretion.
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6. EPIDERMIS
• The outer most layer of skin is made up of stratified
squamous epithelial cells.
• Epidermis is thickest in palms and soles.
• Epidermis layer is made up of epithelial tissue.
• Epidermis skin are present in keratin cells . The keratin
generally release keratin protein.
• The epidermis skin are contain five layer :-
Stratum corneum (Horney layer).
Stratum lucidum (clear layer).
Stratum granulosum (granular layer).
Stratum spinosum (Pricky layer).
Stratum germinativum .
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7. • STRATUM CORNEUM :- The stratum corneum layer is
the top layer of the skin .
• Stratum corneum primarily function as a barrier between the
deeper layer of skin & outside environment preventing toxins
& bacteria from entering the body.
• STRATUM LUCIDIUM :- Stratum lucidum 2-3 cell layers.
• Stratum lucidum layer is only present in the thicker skin of the
palms & soles.
• It’s main function is to reduce friction between the stratum
corneum & stratum granulosum.
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8. • STRATUM GRANULOSUM :- Also called granular layer
• Consist of 3-4 flattened layer of cell.
• These granular release lipids rich secretion, which acts as the
water repellent.
• STRATUM SPINOSUM :- Also called spiny layer.
• Consist 8 to 10 layer of cells & it is closely arranged .
• STRATUM BASALE :- This is innermost layer .
• FUNCTION :- proliferation , attachment of the epidermis of
dermis.
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10. DERMIS
• Dermis is 3 to 5 mm thick layer and is composed of a
matrix of connective tissue , which blood vessels &
nerves.
• It also provide nutrient and oxygen to the skin while
removing toxins and waste products.
HYPODERMIS :-
• The hypodermis is a bottom layer of skin in your body.
• It consist of blood vessels, sensory neurons, some hair
follicles and fat cells.
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11. MERITS
• Avoids first pass hepatic metabolism.
• Decrease the dose of administration.
• Decrease un-wanted/side effects.
• Decrease gastro-intestinal side effects.
• Great advantages for patient who are unconscious.
• Increased patient compliance.
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12. DEMERITS
• Daily dose of more than 10mg is not possible.
• Local irritation is a major problems .
• Uncomfortable to wear.
• Heat, cold, sweating & showering prevents the
patch from sticking to the surface of the skin for
More than one day.
• Drugs large molecular size can not be formulated as
TDDS.
• May not be economical.
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13. MECHANISM OF ABSORPTION THROUGH SKIN.
• Mechanism involved is passive diffusion.
• This can be expressed by FICK’S LAW OF DIFFUSION .
DQ = DKA(C1-C2)
DT H
• Dq/dt = rate of diffusion.
• D= diffusion co-efficient.
• K= partition co-efficient.(liphophilic drug)
• A=Surface area of membrane.
• H= Thickness of membrane.
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14. FACTOR AFFECTING
BIOLOGICAL FACTORS :-
• pH of the skin.
• Skin hydration.
• Site of application.
PHYSICOCHEMICAL FACTORS :-
• Partition co-efficient.
• Molecular size & shape.
• Stability & half – life.
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15. • pH of the skin :-
The pH of the skin is usually acidic 4-6.
• The pH is responsible for regulating permeability of drug.
• According to pH penetration hypothesis, only the un ionised form of
drug can permeate through lipids barrier.
• SKIN HYDRATION :-
Hydration is most important factor
increasing the permeation of skin.
• So use of humectant is done in transdermal delivery.
• SITE OF APPLICATION :-
• The site on which the TDDS patches are
applied will affects the permeation .
• The thicknessn of the skin , nature of startum corneum very site to
site which affects permeation.
BIOLOGICAL FACTORS
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16. PHYSICO CHEMICAL FACTORS:-
• MOLECULAR SIZE & SHAPE :-
Drugs with high
molecular weight have low permeation (<400
daltons) .
• Smaller particle size have more permeability than the
large particle.
• STABILITY & HALF LIFE :-
Drug should be stable when it
comes in contact with the skin .
• It stored have low melting point .
• Half life of drug should be less than 10hrs .
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18. POLYMER MATRIX
• The polymer controls the release of the drug
from the device . Possible useful polymers for
transdermal devices are:-
• Natural polymers:- cellulose derivatives, zein ,
gelatin Shellac, Waxes, Proteins ,Starch etc.
• Synthetic Elastomers:- Polybutadiene , Hydrin
rubber , Polysilicone rubber etc.
• Synthetic Polymers :- Polyamide, Polyvinyl
Pyrrolidone , Epoxy etc.
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19. DRUG
• The drug should have a molecular weight less
than approximately 1000 Daltons.
• The drugs should have affinity for lipophilic
and hydrophilic phases.
• The drug should have low melting point .
• Along with these properties the drug should
be potent, and be nonirritating.
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20. PENETRATION ENHANCHERS
• Increased the absorption of penetrat through the skin.
• This makes the skin more permeable and they allow drug
molecules to cross the skin at a faster rate.
• These are also called absorption promotion.
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21. • These are compounds which promote skin
permeability by altering the skin as a barrier
to the flux desired penetrat .
• Permeation enhancer are incoperated into a
formulation to improve the diffustivity &
solubility of drugs through the skin that would
reversibly reduces the barrier resistances of
the skin .
• These includes water , pyrolidones , fatty
acids & alcohol etc.
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23. ROUTE OF DRUG OF ABSORPTION THROUGH
SKIN.
• TRANS –FOLLICULAR ROUTE:-
• Functional area available through this route is 0.1% drug absorbed.
• Human skin contains 40-70 hair follicles,200-
250sweat glands an every 1sq.cm of skin area.
• Mainly water soluble drug are diffused faster through appendages
that of other layer .
• Easy pathway for diffusion through rate limiting startum corneum.
• This are also called intracellular route.
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25. TRANS-EPIDERMAL ROUTE
• The trans-epidermal pathway involves the passages
of molecules through the stratum corneum.
• The stratum corneum layer by drug molecule may
penetrate either transcellular route.
• In this route the drug absorbed is 99.9%.
• Intracellular region is filled with lipids with
amorphous materials.
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26. FORMULATION :-
• POLYMER MATRIX / DRUG RESERVOIR :-
• The polymer control the release of the drug from the device.
• Polymer matrix can be prepared by dispersion of drug in
liquid or solid state synthetic polymer base.
• Polymer used in TDDS should have good stability &
compatibility with the drug. Ex:- zein , Gelatin , Shellac waxes.
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27. • DRUGS :- The selection of drug for TDDS is based on
physico-chemical property of drugs.
• Extensive first pass metabolism.
• Narrow therapeutic window.
• Dose should be less than (10mg/day)
• Low molecular weight (less than 500 dalton ) .
• Low melting point (less than 200 celsius) .
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28. • Other excipients :-
Various solvents such as
choloroform , methanol, acetone , isopropane &
dicholoromethane are used to prepare drug reservoir
In addition plasthicizer such as :- dibutyl pthalate ,
triethylcitrate , polyethylene , glycol & propylene
glycol are added to provide plasticity to the
transdermal patches.
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31. PHYSICO-CHEMICAL EVALUATION
• THICKNESS :-
With the help of screw gauge thickness is
measured of transdermal film and average is taken.
• DRUG CONTENT :-
An accurately weigh portion of film
(about 100mg) is dissolve in 100ml of suitable solvent in
which drug is soluble continously for 24hrs in shaker
incubator . After sonicated & subsequent filteration , drug
in solution by appropriate dilution is estimated
spectrophotometry.
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32. • UNIFORMITY OF WEIGHT :-
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 weigh in digital balance.
The average weight and standard deviation value are to be
calculated from the individual weights.
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
prepared patch.
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33. IN VIVO EVALUATION
• In vivo evaluation of TDDS can be carried out using
animal model and human model for clinical trials
conducted to determine the drug or device is safe
and effective for people to use.
• There are mainly two types :-
• ANIMAL MODEL
• HUMAN MODEL
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34. IN VIVO EVALUATION
• ANIMAL MODEL :-
Considerable time and
resources are required to carry out human
studies . So animal studies are preferred of small
scale . The most common animal species used for
evaluating transdermal patches are mouse ,
dogs , rehsus, monkey etc . This is one of the
most reliable models for in vitro evaluation of
transdermal patches in animals .
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35. SKIN IRRITATION STUDY
• Skin irritation and sensitization testing can be
performed on healthy rabbits (average weight 1.2
to 1.5kg).
• The dorsal surface (50cm²) of the rabbits is to be
cleaned and removed the hair from the clean
dorsal surface by shaving and clean the surface
by using rectified spirit and the representative
formulation can be applied over the skin.
• The patch is to be removed after 24hrs and the
skin is to be observed and classified into 5 grades
on the basis of the severity of skin injury.
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36. HUMAN MODEL
• The final stage of the development of a
transdermal device involves collection of
pharmacokinetic & Pharmacodynamic data
following application of the patch to human
volunteers.
• Clinicals trials have been conducted to assess
the efficacy , risk involved side effects , patent
compliance etc.
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37. Clinical trials are conducted to determined mainly safety in
volunteers .
PHASE 1 :-
Clinical trials are conducted to determined mainly safety
in volunteers.
PHASE 2 :-
Clinical trials determined short term safety & mainly
effectiveness in patients .
PHASE 3 :-
Trials indicate the safety and effectiveness in large
number of patient population.
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38. Approaches to development of transdermal
therapeutic systems .
• A transdermal patch is a medicated adhesive patch that is
placed on the skin to deliver a time – released dose of
medication through the skin and into the bloodstream.
• Types of TDDS/ Approaches in development of
TDDS :-
• Membrane permeation controlled systems/reservoir
type systems.
• Adhesive – dispersion type systems.
• Matrix diffusion – controlled systems.
• Microreservoir controlled drug delivery systems.
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39. PHASE 4 :-
Trials at post marketing surveillance are done for
marketed patches to detected ADRs.
Human studies required considerable resource but they are
the best to assure the performance the drugs.
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40. FORMULATION APPROACHES
POLYMER MEMBRANE PERMEATION CONTROLLED(TDDS)
It is a type of system in which drug is dispersed in solid
polymer matrix form drug reservoir .
The drug released only through the rate-controlling
membrane which can be micro-porous or non-porous .
Ex:- Nitroglycerine –releasing Transdermal system
(Transdermal-nitro) for once a day medication in angina
pectoris.
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41. ADHESIVE DISPERSION TYPE SYSTEM
• The drug reservoir is formed by dispersing the drug in an adhesive
polymer & then spreading the medicament polymer adhesive by
solvent casting or by melting the adhesive(in case of hot-melt
adhesive)on to an impervious backing layer.
• Ex:- Isoborbide dinitrate –releasing transdermal therapheutic
system (Frandol tape )for once a day medication of angina pectoris.
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42. MATRIX DIFFUSION CONTROLLED SYSTEM
• The drug is dispersed homogenously in a hydrophilic or
lipophilic polymers matrix.
• The contaning polymer disk then is fixed onto an occlusive
base plate in a compartment fabricated from a drug-
impermeable backing layer. Ex:- Nitro Du(Nitroglycerine)used
for once a day medication of angina pectoris.
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43. MICRO-RESERVOIR CONTROLLED (TDDS)
• The drug delivery system is a combination of reservoir &
matrix –dispersion system.
• The drug reservoir is formed by first suspending the drug in an
aqueous solution of water soluble polymer & then dispersing
the solution homogenously in a lipophilic polymer to form
thousands of un-reachable , microscopic sphere of drug
reservoir.
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44. EXAMPLE :-
• Nitroglycerine – releasing Transdermal system
(Nitro-disc) for once a day therapy of angina
pectoris.
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45. REFERNCES
• M.H. Qvist et al.Release of chemical
penetration enhancers from drug-in-adhesive
transversal patches ,Int. J. Pharm (2002).
• M.A. Repka et al.Bioadhesive properties of
hydroxypropylcellulose topical films produced
by hot-melt extrusion,J. Control. Releas(2001).
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