This document provides an overview of transdermal drug delivery systems (TDDS). It discusses the advantages and limitations of TDDS, skin structure, components of transdermal patches, types of patches, factors affecting transdermal permeability, polymers used, therapies that use TDDS, classification of TDDS, basic components, evaluation, and drug release mechanisms. The document contains detailed information on formulation, evaluation parameters, in vitro and in vivo testing of TDDS.

1. TRANSDERMAL DRUG DELIVERY SYSTEM
1
MALLA REDDY COLLEGE OF
PHARMACY
GUI DANCE: Dr .YASMI N BEGUM
PRESENTI ED BY,
P.RAJ I THA
256213886026

2. CONTEN
TS
 INTRODUCTION
 ADVANTAGES AND LIMITATIONS
 SKIN AND EPIDERMIS STRUCTURE
 COMPONENTS OF TRANSDERMAL PATCH
 TYPES OF TRANSDERMAL PATCH
 FACTORS AFFECTING TRANSDERMAL PERMEABILITY
 POLYMERS
 THERAPIES THAT USE TRANSDERMAL DELIVERY OF DRUGS
 CLASSIFICATION OF TDDS
 BASIC COMPONENTS OF TDDS
 EVALUATION
 CONCLUSION
 REFERENCE
2

3. I NTRODUCT
I ON  Tr ansdermal deliver y r epr esent s an
at t r act ive alt er nat ive t o or al deliver y of
dr ugs and is poised t o pr ovide an alt er nat ive
t o hypodermic inj ect ion t oo.
 For t housands of year s, people have placed
subst ances on t he skin f or t her apeut ic
ef f ect s.
Def init ion:
Tr ansdermal dr ug deliver y syst ems (pat ches)
ar e dosage f orms designed t o deliver a
t her apeut ically ef f ect ive amount of dr ug
3
acr oss a pat ient ’s skin also def ined as

4. 4
The Present Day
• 1970-- Alza Research (US) began first
development of the modern transdermal
• 1980-- Scopolamine first transdermal reached
US
• 2002– Many Rx and non-RX products in US
market.
• Transdermals deliver drugs from a few hours
up to 7 days.
09/30/14

5. Advant ages of
TDDS
 Reduces f ir st -pass met abolism ef f ect
and GI incompat ibilit y
 Sust ains t her apeut ic dr ug levels
 Permit s self -administ r at ion
 Non-invasive (no needles or
inj ect ions)
 I mpr oves pat ient compliance
 Reduces side ef f ect s
 Allows r emoval of dr ug sour ce
 Long act ing dr ug deliver y 5

6. Limit at ions of
TDDS
 Poor dif f usion of lar ge molecules
 Skin ir r it at ion
 Only suit able f or ver y pot ent dr ugs
 Mor e expensive t han or al dr ugs
6

7. Skin st r uct ur e
7
EPIDERMIS
STRUCTURE

8. Component s of Tr ansdermal
Pat ch.
1. Liner - Pr ot ect s t he pat ch dur ing
st or age.
2. Drug - Dr ug solut ion in dir ect cont act
wit h r elease liner .
3. Adhesive - Ser ves t o adher e t he
component s of t he pat ch t oget her along
wit h adher ing t he pat ch t o t he skin.
4. Membrane - Cont r ols t he r elease of
t he dr ug.
5. Backing - Pr ot ect s t he pat ch. 8

9. TYPES OF TRANSDERMAL PATCHES
(1) Single- layer Drug- in- Adhesive: The
adhesive layer of t his syst em also cont ains
t he dr ug.
(2) multi- layer drug in adhesive: One of t he
layer s is f or immediat e r elease of t he dr ug
and ot her layer is f or cont r ol r elease of dr ug
f r om t he r eser vior .
(3) Reservoir:
(4) Matrix: The Mat r ix syst em has a dr ug
layer of a semisolid mat r ix cont aining a dr ug
solut ion or suspension.
9
The dr ug layer is a liquid compar tment
cont aining a dr ug solut ion or suspension
separ at ed by t he adhesive layer

10. Fact or s ef f ect ing t r ansdermal
permeabilit y
(A) Physicochemical pr oper t ies of t he
penet r ant s:
1. Par t it ion coef f icient .
2. PH condit ions.
3 . Penet r ant concent r at ion.
(B) Physicochemical pr oper t ies of dr ug deliver y
syst ems:
1. Release char act er ist ics.
2. Composit ion of dr ug deliver y syst ems-
3. Enhancement of t r ansdermal penet r at ion.
(C) Physiological and pat hological condit ions of
t he skin
10

11. Polyme
Polyrmse:r s ar e t he backbone of a
t r ansdermal dr ug deliver y syst em.
Syst ems f or t r ansdermal deliver y ar e
f abr icat ed as mult i-layer ed polymer ic
laminat es in which a dr ug r eser voir or a
dr ug polymer mat r ix is sandwiched
bet ween t wo polymer layer s an out er
imper vious backing layer t hat pr event s
t he loss of dr ug t hr ough t he backing
sur f ace.
Examples :HPMC 100, CMC, Polyet hylene glycol,
polycar bonat e, PVA, Polycar bonat e, Sodium
11

12. Ther apies That Use
Tr ansdermal
Deliver y of
Dr ugs
12
Therapy Drug Delivered by
TDDS
Mot ion Sickness Scopolamine
Ant i-angina Nit r oglycer ine
Hypertension Clonidine
Smoking Cessat ion Nicot ine
Hormone Replacement
Ther apy
Est r adiol
Est r adiol/ Pr ogest in
Test ost er one
Pain Management Fent anyl
Lidocaine

13. Classif icat ion of
TDDS
13
1. Polymer membrane permeation-controlled.
2. Polymer matrix dif fusion-controlled
3. Drug reservoir gradient- controlled
4. Micro reservoir dissolution-controlled

14. Formulation of TDDS
1.Membrane-moderated or permeation controlled TDDS
• Drug reservoir(homogenous dispersion of drug with polymeric matrix or
suspension of drug in un leachable viscous liquid medium such as silicone fluid) is
encapsulated within drug impermeable metallic plastic laminate and a rate
controlling polymeric membrane(ethylene vinyl acetate co polymer)
• The cross sectional view of this system is shown in the following Fig.1
14

15. • A thin layer of silicone or poly acrylate adhesive may be applied to the external
surface of the rate controlling membrane to achieve intimate contact of the TDDS
and the skin surface
• Release rate of this TDDS depends upon the polymer composition,permeability co
efficient and thickness of the rate cotrolling membrane and adhesive
• The intrinsic rate of drug release from this TDDS is calculated by the following
formula.1
CR
dQ/dt= --------------------
1/Pm+1/Pa
CR-con.of drug in the reservoir compartment
Pm-permeability co efficient of rate controlling polymeric
membrane
Pa- permeability co efficient of adhesive
15

16. 2.Adhesive diffusion/dispersion-controlled TDDS
Drug reservoir
• homogenous dispersion of drug with adhesive polymer(poly(isobutylene) or poly
acrylate)
• Then spreading of this medicated adhesive polymer on flat sheet of drug
impermeable metallic plastic backing to form thin drug reservoir layer
• On top of the drug reservoir layer,thin layers of rate controlling adhesive polymer
of specific permeability and constant thickness are applied to produce an adhesive
diffusion/dispersion-controlled TDDS
• The cross sectional view of this system is shown in the following Fig.2
16

17. • The rate of drug release in this system is defined by
Ka/r.Da
dQ/dt= -----------------CR
ha
Where
Ka/r-partition co-efficient of drug bw adhesive layer and reservoir layer
Da-diffusion co-efficient of drug in the adhesive layer
ha-thickness of adhesive layer
Examples for this system
1.Iso sorbide dinitrate-releasing TDDS
2.Verapamil releasing TDDS
17

18. 18
• 3.Matrix diffusion-controlled TDDS
Drug reservoir
• homogenous dispersion of drug with hydrophilic or lipophilic polymer matrix by any one of
the following methods
• Homogenous dispersion of finely ground drug particles with liquid polymer or highly viscous
base polymer followed by cross linking of polymer chains
• Homogenous mixing of drug solid with rubbery polymer at an elevated temperature
• Dissolving the drug and polymer in a common solvent follwed by solvent evaporation in a
mould at an elevated temperature or under vaccum.
• Medicated polymer is moulded in to desired surface area and controlled thickness
• This medicated polymer disc is pasted on to an occlusive base plate with impermeable plastic
backing
• Then the adhesive polymer is spread along the circumference to form a strip of adhesive rim
around the medicated disc

19. • the rate of drug release from this sytem is defined as
A Cp Dp
Dq/dt = [ ---------------------] 1/2
2t
where
A initial drug loading dose
Cp and Dp are solubility and diffusivity of drug in poymer matrix
the rate of drug release from this system at steady state is defined as
Q/t1/2= [(2A-Cp) Cp Dp] 1/2
19

20. Example of this system are
1.Nitro glycerin releasing TDDS (Nitro-Dur and Nitro-Dur II /Key pharmaceuticals,USA)
2. Estradiol di acetate releasing TDDS
3. Verapamil releasing TDDS
The cross sectional view of this system is shown in the following Fig.3
20

21. 4.Micro reservoir type/micro sealed dissolution- controlled
TDDS
Combination of the reservoir and matrix diffusion
Drug reservoir
•suspension of drug with aqueous solution of water soluble liquid polymer
•Homogenous dispersion of drug suspension in a lipophilic polymer(silicone elastomer)
•As a result discrete un leachable microscopic spheres of drug reservoir is formed which is stabilized
by cross linking
•Medicated polymer is moulded in to desired surface area and controlled thickness and it is coated
with a layer of bio compatible polymer to modify mechanism and rate of drug release
•This medicated polymer disc is pasted on to an occlusive base plate with impermeable plastic backing
•Then the adhesive polymer is spread along the circumference to form a strip of adhesive rim around
the medicated disc
Example of this system are
1.Nitro glycerin releasing TDDS (Nitrodisc /searle,USA)
21
The cross sectional view of this system is shown in the following Fig.4

22. 22

23. 23
TTS Available in market
Large scale mfg of TTS

24. 24
Evaluation Parameters
Physical parameters
Evaluation of adhesive
In-vitro testing
In-vivo assessment
Cutaneous metabolism
Stability studies
Evaluation of skin reactions.
09/30/14

25. 25
Thickness
09/30/14

26. 26
Weight variation
09/30/14

27. 27
Folding endurance
09/30/14

28. 28
09/30/14 Moisture content
% Moisture content = Initial weight – Final weight X 100
Final weight

29. 29
Moisture uptake
09/30/14 % moisture uptake = Final weight – Initial weight X 100
Initial weight

30. 30
Flatness
09/30/14 % constriction = I1 – I2 X 100
I1
I2 = Final length of each strip
I1 = Initial length of each strip

31. 31
Drug content
09/30/14

32. 32
Water Vapor Transmission studies
09/30/14

33. 33
Evaluation of adhesive
1} Peel adhesion
properties
It is the force required to remove adhesive from test substrate.
09/30/14

34. 34
2} Tack properties
It is the ability of the polymer to adhere to substrate with little contact
pressure.
2.1} Thumb tack test
2.2} Rolling ball tack test
09/30/14

35. 35
2.3}Quick-stick (or peel-tack)
test
09/30/14

36. 36
2.4} Probe tack
test
09/30/14

37. Shear strength is the measurement of the cohesive strength of adhesive polymer.
37
3} Shear strength properties
09/30/14

38. 38
Tensile strength
09/30/14 Tensile strength= F/a.b (1+L/l)
F - the force required to break
a - width of film
b - thickness of film
L - length of film
l - elongation of film at break point

39. 39
In-vitro testing
The Paddle over Disc
The Cylinder modified USP Basket
The reciprocating disc
Diffusion Cells e.g. Franz Diffusion Cell and its modification Keshary-
Chien Cell
09/30/14

40. 40
In-vitro testing
Importance
(1)Defining skin permeation kinetic studies using a
diffusion cell system and cadaver skin during the drug
development process.
(2) in vitro drug release kinetics, to be used for batch-to-
batch release and as a compendial test.
09/30/14

41. Preparation of skin for permeation studies
• Intact Full thickness skin
• Separation of epidermis from full thickness
skin:
41

42. 42
K-C cell for permeation studies
09/30/14

43. 43

44. Effect of skin uptake metabolism
44

45. 45
In-vivo assessment
1} Animal model
Mouse, hairless rat, hairless dog, hairless rhesus monkey,
rabbit, guinea pig
09/30/14

46. 46
In-vivo assessment
2} Human model
. Phase I clinical trials are conducted to determine mainly safety in
volunteers.
Phase II clinical trials determine short term safety and mainly effectiveness
in patients.
 Phase III trials indicate the safety and effectiveness in large number of
patient population.
Phase IV trials at post marketing surveillance are done for marketed
patches to detect adverse drug reactions.
09/30/14

47. Skin irritation studies
• Group I was served as normal, without any
treatment.
• Group II, control, was applied with marketed
adhesive tape.
• Group III Transdermal systems (blank)
• Group IV Transdermal systems (drug loaded)
• Group V standard irritant .
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Contact dermatitis

48. 48
Evaluation of skin reactions.
09/30/14

49. 49
Stability studies
09/30/14

50. Study Storage conditions Time period
Temperature Relative
humidity
Long Term 25°C± 2°C
OR
30°C± 2°C
60%± 5%
OR
65%± 5%
12 months
Intermediate 30°C± 2°C 65%± 5% 6 months
Accelerated 40°C± 2°C 75%± 5% 6 months
50

51. Based on mechanism of act ion
TDDS-t ypes
(1) Solut ion in mat r ix
(2) Suspension in cont inuous mat r ix
(3) Suspension in por ous mat r ix
(4) Solut ion upst r eam of membr ane
(5) Suspension upst r eam of membr ane
(6) Laminat ed membr ane downst r eam
51

52. DRUG RELEASE
MECHANI SM
1) I ont ophor esis:
52
I t is an elect r ochemical met hod
t hat enhances t he t r anspor t of some
solut e molecules by cr eat ing a
pot ent ial gr adient t hr ough t he skin
wit h an applied elect r ical cur r ent or
volt age.
2)Elect r opor at ion:
I t is a met hod wher e high volt age
elect r ical pulses supplied t o t he skin.

53. I ont ophor esis
53
Non-invasive, needle-f r ee
Rapid onset and cessat ion kinet ics
Cont r olled, pr ogr ammable and
t it r at able dr ug deliver y capabilit ies
Abilit y t o pr ovide smoot h, var iable
or bolus plasma levels, singly or in
combinat ion, all in a single deliver y
syst em
Enhanced t r ansdermal deliver y f or a
br oad r ange of compounds, including
lar ge dr ug molecules such as
pept ides and oligonucleot ides
Minimal var iabilit y in t he deliver y
pr of iles among pat ient s and body

54. SCIENTIFIC BASIS OF
IONTOPHORESIS
The Ner nst -Planck equat ion, seen below, is t he
t r adit ional r elat ionship accept ed f or descr ibing
t r anspor t of an ionic species acr oss a membr ane:
J = DzVFC/ kT+ Cu - D(dC/ dx)
wher e J = molar f lux
D = dif f usivit y coef f icient
C = t he concent r at ion (molar )
u = t he convect ive f low of wat er
T = t emper at ur e
k = Bolt zman' s const ant
z = char ge on t he species
V = elect r ic f ield
54

55. Phonophor esis
Phonophor esis is t he int r oduct ion of subst ances int o t he
body by ult r asonic ener gy. Unlike iont ophor esis which
involves t he t r ansf er of ions int o t he t issue,
phonophor esis t r ansmit s molecules a dif f er ent pr ocess
alt hough similar in concept .
Some of t he common chemicals compounded f or
phonophor esis include:
55
·Bet amet hasone Dipr opionat e
·Dexamet hasone
·Dexamet hasone / Lidocaine
·Fluocinonide
·Hydr ocor t isone
·Hydr ocor t isone / Lidocaine
·Ket opr of en / Napr oxen

56. How it wor ks
56

57. Conclusion:
 Due t o t he r ecent advances in t echnology and
t he incor por at ion of t he dr ug t o t he sit e of
act ion wit hout r upt ur ing t he skin membr ane
t r ansdermal r out e is becoming t he most
widely accept ed r out e of dr ug administ r at ion.
 I t pr omises t o eliminat e needles f or
administ r at ion of a wide var iet y of dr ugs in
t he f ut ur e.
 To opt imize t his dr ug deliver y syst em,
gr eat er under st anding of dif f er ent
mechanism of biological int er act ions, and
polymer s ar e r equir ed.
57

58. Ref er ences:
1..Williams A. London: Pharmaceut ical Pr ess; 2003.
Tr ansdermal and Topical Dr ug Deliver y.
2. Pr ausnit z MR, Mit r agot r i S, Langer R. Cur r ent
st at us and f ut ur e pot ent ial of t r ansdermal dr ug
deliver y.t Rev Dr ug Discov. 2004;3:115–124.
3. Br onaugh RL, Maibach HI , edit or s. Edn. 4t h. New
Yor k: Mar cel Dekker ; 2005. Per cut aneous Absor pt ion.
4. Miller MA, Pisani E. The cost of unsaf e inj ect ions.
Bull Wor ld Healt h Or gan. 1999;77:808–811.
5. Ault on.M.E, Pharmaceut ics; The science of dosage
f orm design, second edit ion, Chur chill Livingst on,
Har cour t publisher s-2002.
6. Ansel.H.C, Loyd.A.V, Popovich.N.G, Pharmaceut ical
dosage f orms and dr ug deliver y syst ems, Sevent h
58

59. • Scheindlin Stanley Transdermal drug delivery: PAST,
PRESENT, FUTURE. Molecular interventions (2004),
4(6), 308-12 (see link in presentation).
• Prausnitz, Mark R.; Langer, Robert. Transdermal drug
delivery. Nature Biotechnology (2008), 26(11),
1261-1268 Link
• Sieg, A.; Wascotte, V. Diagnostic and therapeutic
applications of iontophoresis. Journal of Drug
Targeting, (2009); 17(9): 690-700.
• Graduate Students Only: Subedi, R. K. et al. Recent
Advances in Transdermal Drug Delivery. Archives of
Pharmal Research (2010), 33(3): 339-351.
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60. THANK YOU
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