presentation on TDDS

1. TRANSDERMAL DRUG
DELIVERY SYSTEM

2.  Transdermal systems are defined as self-contained, discrete dosage forms which,
when applied to the intact skin, delivers the drug through the skin at a controlled
rate to the systemic circulation

3. ADVANTAGES
Delivers a steady infusion of a drug over an extended period of time.
Less fluctuations
Increases the therapeutics value of many drugs by avoiding various problems like:
• GI irritation
• Low oral absorption
• First pass metabolism
• Short half life
• Formation of metabolites that cause side effects
Lower dose than oral dosing
Improved patient compliance
Termination of therapy possible
Self administration is possible

4. LIMITATIONS
Drugs should penetrate the stratum corneum.Thus only small
lipophilic drugs can be delivered currently
Dose required if more than – 20 mg/day –TDDS difficult
Skin irritation or contact dermatitis due to drug, excipients and
permeation enhancers
The barrier function of skin changes from one site to another on the
same person, from person to person and with age
Inter and intra-patient variability is high

5. CROSS-SECTION OF SKIN

6. SKIN
Most extensive organ in the body
Covers an area is 2 m2
Receives 1/3rd of all blood circulating
Thickness – 1 mm

7. EPIDERMIS
Outermost layer
Thickness – 150 µm
Various
layers
Stratum corneum – stratified and extremely resilient
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum basale

8. STRATUM CORNEUM
Horny layer
Rate limiting barrier that restricts the entry and
exit of chemical substances
15 – 25 layers of flattened polygonal cells
Interiors of these cells is crisscrossed with densely
packed bundles of keratin fibers
Thus it has 75 – 85% proteins (intracellular)
Remaining is lipids (intercellular)

9. DERMIS
Thick – 2000 µm
80% protein (collagen)
On a matrix of muco-polysaccharide (ground
material)
A rich bed of capillaries 20 µm deep
Also contains – lymph capillaries, nerves, hair
follicles, sebaceous glands and sweat glands

10. PERCUTANEOUS DRUG
ABSORPTION
10

11. EVENTS GOVERNING PERCUTANEOUS
ABSORPTION
11

12. 2 MODES OF PERCUTANEOUS DRUG
ABSORPTION
Criteria Transepidermal Transfollicular
Site for drug permeation Stratum corneum Pilosebaceous unit
Diagrammatic
representation
Importance of the route in
drug permeation
Major route Secondary route
Classification Intracellular and intercellular Via hair follicles, sebaceous glands and
ecrine sweat glands (negligible)
Drugs have to partition
through
Protein-lipid matrix of stratum
corneum
Sebum

13. Number of times the drug has to
diffuse
Lot of times. It requires frequent
crossings of cell membrane
Just once.Through the lipids in
sebaceous pores
Thickness of barrier layer Thicker. Almost 1 µm Thinner. Approximately 10-3 µm
Fraction of surface area of skin
available for drug permeation
1 0.001
Duration of drug permeation Drugs are absorbed over a longer
duration
Shows transient diffusion of drugs
Lag time for drug absorption Small molecules gets absorbed in
minutes whereas large molecules may
even take days to get absorbed
The lag time ranges from seconds to a
few minutes
Steady state flux Higher. Flux observed by this route is
30 times as compared to
transfollicular route
Lower flux
Dedicated pharmacokinetic models Available Not available

14. Equation describing kinetics of drug
permeation
RTransepidermal = Rstratumcorneum + Rviable tissue-
TransEpidermal
RTE = RSC + Rvt-TE
Where R = resistance offered
RTransfollicular = Rsebum + Rviable tissue-
TransFollicular
RTF = RSeb + Rvt-TF
Where R = resistance offered
Preferred by type of drug Both hydrophilic and lipophilic drugs
can pass through
Suitable for small hydrophilic non-
electrolyte molecules
Examples of drugs known to
permeate via the route
Clonidine, fentanyl, nicotine,
nitroglycerine, estradiol, scopolamine,
testosterone etc
Nitroglycerine, estradiol etc
Important characteristic of drug
which makes it a suitable candidate
HLB Small size, uncharged and hydrophilic
Preferred vehicles Oily vehicles like oleic acid or
petrolatums
Polar vehicles like propylene glycol,
ethanol etc
Preferred dosage forms Topical semisolids likes ointments, gels
etc and transdermal patches
Liposomes and other small colloidal
carriers
Drug permeation affected by Dry skin, psoriasis, UV rays etc Alopecia, hirsutism, hypertrichosis etc
Beneficial for Systemic drug delivery (major), skin
infections etc
Systemic drug delivery (minor), acne
etc

15. FACTORS AFFECTING
TRANSDERMAL PERMEATION
15

16. 16
Biological
factors
Skin conditions
Skin age
Blood Supply
Regional skin site
Skin metabolism
Species differences
Skin hydration
Temperature
pH
Physicochemical
factors
Diffusion coefficient
Drug concentration
Partition coefficient
Molecular size and shape
Melting point

17. BIOLOGICAL FACTORS
• Intact skin is an effective barrier but any kind of skin damage or injury
may allow more drug to permeate
Skin conditions
• Skin of adults and young ones are more permeable than the older ones
• Children shows toxic effects because of the greater surface area per
unit body weight
Skin age
• Changes in peripheral circulation can affect transdermal absorption
Blood supply
17

18. • Thickness of skin, nature of stratum corneum and density of appendages
vary site to site
• These factors affect penetration significantly
Regional skin
site
• Skin metabolizes steroids, hormones, chemical carcinogens and some drugs
• So skin metabolism determines efficacy of drug permeated through the skin
Skin metabolism
• The skin thickness, density of appendages and keratinization of skin vary
species to species, so that affects the penetration
Species
differences
18

19. • In contact with water the permeability of skin increases significantly
• So use of humectant is done in transdermal delivery
Skin hydration
• The permeation of drug increases up to ten folds with temperature
variation
Temperature
• Weak acids and weak bases dissociate depending on the pH and pKa or pKb
values
• The proportion of unionized drug determines the drug concentration in skin
pH
19

20. PHYSICOCHEMICAL FACTORS
• At a constant temperature the diffusion coefficient of drug depends on
properties of drug, diffusion medium and interaction between them
Diffusion coefficient
• The flux is proportional to the concentration gradient across the barrier
Drug concentration
• Drugs with high partition coefficient do not leave the lipid portion of skin (>3)
• Drug with low partition coefficient will not be able to permeate effectively (<1)
Partition coefficient
• Drug absorption is inversely related to molecular weight
Molecular size and shape
• Drugs with high melting points (>150°C) have relatively high lipid solubility
hence better permeation
Melting point
20

21. BASIC COMPONENTS OF TDDS

22. Basic
components of
TDDS
Drug
Polymer
matrix
Permeation
enhancers
Adhesives
Backing
membrane
Release
liner

23. DRUG - DESIRABLE PROPERTIES
Physicochemical
properties
Mol wt <
1000 daltons
HLB
Low melting
point
Biological
properties
Potent (dose
< 10 mg/day)
Half life –
short
Not
cutaneous
irritant

24.  Ideal properties of drugs forTDDS

25. POLYMER MATRIX - IDEAL
CHARACTERISTICS
Molecular weight, glass transition temperature and chemical functionality of the polymer should be such
that the drug diffuses properly and gets released through it
Should be stable, non-reactive with the drug
Should be easily manufactured and fabricated into desired product
Inexpensive
Polymer and its degradation products must be non-toxic to the host
Mechanical properties of the polymer should not deteriorate excessively when large amounts of drug is
incorporated

26. Polymer
Natural polymers
Cellulose derivatives,
zein, shellac, waxes,
gums, starch, rubber
Synthetic elastomers
Polybutadiene,
polysiloxane, butyl
rubber, neoprene
Synthetic polymers
PVA, PVC, PE, PP,
polyamide, PVP,
PMMA
Types

27. PERMEATION ENHANCERS
 They promote skin permeability by altering the skin as a barrier to
the flux of a desired permeant
 The enhancement of flux across membrane reduces to
considerations of:
 Thermodynamics (lattice energies, distribution coefficients)
 Molecular size and shape
 Reducing the energy required to make a molecular hole in the
membrane

28.  Ideal properties of penetration enhancers
1. Controlled and reversible enhancing action
2. Chemical and physical compatibility with drug and other pharmaceutical
excipients
3. Should not cause loss of body fluids, electrolytes or other endogenous
materials
4. Non toxic, non allergic, non irritating
5. Pharmacological inertness
6. Ability to act specifically for predictable duration
7. Odorless, colorless, economical and cosmetically acceptable.

29. MECHANISMS OF PENETRATION ENHANCERS
35

30. • Swell polar pathway or fluidize lipids
• Alcohols, DMSO, azone, PG
Solvents
• Enhance polar pathway transport
• Skin irritants
Surfactants
• Relatively safe
• Sadium taurocholate, sodium deoxycholate, sodium tauroglycocholate
Bile salts
• PG-oleic acid, 1,4-butanediol – linoleic acid
Binary systems
• Urea, calcium thioglycolate
Miscellaneous

31. ADHESIVES
 Ideal properties:
 Should not irritate or sensitize the skin
 Should adhere to skin aggressively during the dosing interval without its position
being disturbed by activities such as bathing, exercise etc.
 Should be easily removed
 Should not leave an unwanted residue on the skin
 Should have intimate contact with the skin
 Physically and chemically stable with drugs and other excipients
 Should not affect permeation of drug
 Examples – polyisobutylene, acrylics and silicones

32.  Mechanism of Adhesion: these are also known as “Pressure-sensitive” adhesives (PSA)
 The PSA will adhere to a substrate, in this case skin, because of interatomic and
intermolecular attractive forces established at the interface, provided that intimate contact is
achieved
 To obtain this degree of contact, the material must be able to deform under slight pressure,
giving rise to the term ‘‘pressure sensitive”.
 Adhesion involves a liquid-like flow resulting in wetting of the skin surface upon the
application of pressure, and when pressure is removed, the adhesive sets in that state
 A PSA wets and spreads onto skin when its surface energy is less than that of skin
 After the initial adhesion, the PSA/skin bond can be built by stronger interactions (e.g.
hydrogen bonding), which will depend on skin characteristics and other parameters

33. BACKING MEMBRANE
 Ideal properties
 Should be flexible
 Provide good bond to the drug reservoir
 Prevent drug from leaving the dosage form from top
 Accept printing
 Impermeable
 Eg. Metallic plastic laminate, plastic backing with absorbent pad and
aluminum foil, adhesive foam pad with aluminum foil

34. RELEASE LINER
 During storage release liner prevents the loss of drug that has migrated into the
adhesive layer and contamination
 However, as the liner is in intimate contact with the delivery system, it should
comply with specific requirements regarding chemical inertness and permeation
to the drug, penetration enhancer and water
 It has to be removed before use

35. OTHER EXCIPIENTS
Tackifier
• Chemical compounds used
in formulating adhesives to
increase the tack, the
stickiness of the surface of
the adhesive.
• They are usually low-
molecular weight
compounds with high glass
transition temperature
• Eg. Rosin esters,
hydrocarbon resins, terpene
resins
Plasticizer
• Provide plasticity to the
transdermal patch
• Eg. dibutylpthalate,
propylene glycol
Solvent
• Used to dissolve the
polymer and adhesive
• Eg. chloroform, methanol,
acetone, isopropanol, and
dichloromethane
41

36. NORMALTRANSDERMAL PATCH

37. TDDS
Membrane
permeation
controlled systems
Adhesive
dispersion type
systems
Matrix diffusion
controlled systems
Micro-reservoir
type
Approaches

38. MEMBRANE PERMEATION-CONTROLLED
SYSTEMS
• Totally encapsulated in a shallow compartment
molded from drug-impermeable metallic plastic
laminate
Drug reservoir
• Microporous or non-porous
• Eg ethylene vinyl acetate copolymer (EVA)
Rate controlling
membrane
• Silicone or polyacrylate adhesive
Adhesive

39. Drug
Solid drug dispersed in solid
polymer matrix
Solid drug suspended in an
unleachable viscous liquid
medium eg silicone oil to
form a paste-type
suspension
In reservoir compartment

40. Rate of drug
release
Polymer
composition
Permeability
coefficient
Thickness of rate
limiting
membrane
Thickness of
adhesive
Depends on

41. PROS AND CONS
Constant
rate of drug
release
Accidental
breakage can
lead to dose
dumping

42. INTRINSIC RATE OF DRUG RELEASE
𝑑𝑄
𝑑𝑡
=
𝐶𝑅
1
𝑃𝑚
+
1
𝑃𝑎
−−−−−−−−−− −(6)
 Where;
 Cr – drug conc in reservoir compartment
 Pm – permeability coefficient of the rate controlling membrane
 Pa – permeability coefficient of the adhesive layer

43. 𝑃𝑚 =
𝐾𝑚/𝑟𝐷𝑚
ℎ𝑚
--------------------------- (7)
𝑃𝑎 =
𝐾𝑎/𝑚𝐷𝑎
ℎ𝑎
---------------------------- (8)
 Where;
 Km/r and Ka/m – partition coefficients for the interfacial partitioning of drug from reservoir to
the membrane and from the membrane to the adhesive respectively
 Dm and Da – diffusion coefficients in the rate controlling membrane and adhesive layer
respectively

44.  Substituting equations (7) and (8) for Pm and Pa in equation (6), we get:
𝑑𝑄
𝑑𝑡
=
𝐾𝑚/𝑟𝐾𝑎/𝑚𝐷𝑚𝐷𝑎
𝐾𝑚/𝑟𝐷𝑚ℎ𝑎 + 𝐾𝑎/𝑚𝐷𝑎ℎ𝑎
𝐶𝑅
 Where;
 dQ/dt – intrinsic rate of drug release from a membrane modulated drug delivery system

45. EXAMPLES
• Transderm-Nitro (Ciba)
• Once a day for angina pectoris
Nitroglycerine
• Transderm-Scop (Ciba)
• 72 hrs prophylaxis of motion sickness
Scopolamine
• Catapres – Boehringer Ingelheim
• 7 days therapy for hypertension
Clonidine
• Estraderm – Ciba
• 3 – 4 days for treatment of menopausal syndrome
Estradiol

46. PRODUCTION
Membrane
permeation-
controlled systems
Multi-laminate
products
Transderm-Scop,
Catapress
Form-Fill-Seal
products
Transderm-Nitro,
Estraderm

47. GENERAL METHOD OF PRODUCTION
Such product consists of
three substrates held
together by two layers
containing the drug
The drug, excipients, and
polymers (adhesive) are
mixed thoroughly with a
solvent to produce a uniform
mixture (solution or
dispersion)
The solvent is removed by
drying the mixture
The dried adhesive layers and
the other layers are
laminated. (Total 5 layers)
The five layers are: release
linear, contact adhesive, a
control membrane, the drug
reservoir, and backing
membrane
All the layers are cut into
required size using a die and
printed
The products thus prepared
are packed individually in an
aluminum foil pouch

48. MULTI-LAMINATETDDS
Release liner Backing
Control membrane

49. FORM-FILL-SEAL PROCESS
Backing
substrate
Drug gel
preparation

50. ADHESIVE DISPERSIONTYPE SYSTEMS
The drug is dispersed in an
adhesive polymer such as poly
(isobutylene) or poly (acrylate) to
prepare drug reservoir
This type of system is prepared by
solvent casting or hot melt
method and put over a flat,
metallic plastic membrane
The metallic membrane (foil) is
coated with a plastic material
which is impermeable to drug
The whole of metallic-plastic
membrane forms a thin casing for
holding the drug dispersed in the
adhesive polymer
Thin layers of non-medicated,
rate-controlling adhesive polymer
are applied over the top of the
drug-reservoir layer
The adhesive layer should have a
specific permeability and should
provide uniform thickness
throughout the layer; so that an
adhesive diffusion-controlled
delivery of the drug is possible

51.  The rate of drug release dQ/dt, can be
expressed as:
𝑑𝑄
𝑑𝑡
=
𝐾𝑎/𝑟. 𝐷𝑎
ℎ𝑎
𝐶𝑟
 Where,
 Ka/r is permeation coefficient for the
interfacial partitioning of the drug from the
reservoir layer to adhesive layer
57

52. METHOD OF PREPARATION
58
Preparation of individual matrix solution
Coating of the individual matrix layer
Multilayer lamination
Punching of laminated roll/making unit dose
Packaging

53. MATRIX DIFFUSION-CONTROLLED SYSTEM
The drug reservoir is a
dispersion of drug particles
within a polymer matrix
This is done by
homogeneously dispersing
finely powdered drug in a
liquid polymer or rubbery
polymer at a higher
temperature
The dispersion is thoroughly
mixed by continuous stirring
This can be alternatively done
by dissolving the drug and
polymer in a particular
solvent
The solvent is then
evaporated in a mold at a
higher temperature or under
vacuum
The drug matrix discs are
pasted onto an occlusive base
plate in a compartment
fabricated from a drug
impermeable plastic backing
The adhesive polymer is then
spread along the
circumference to form a strip
of adhesive rim around the
medicated disc
59

54.  The rate of drug release from this type of transdermal system can be expressed
as:
𝑑𝑄
𝑑𝑡
=
𝐴𝐶𝑝𝐷𝑝
2𝑡
1/2
Where,
 A is the dose of drug dispersed in the polymer matrix
 Cp and Dp are solubility and diffusivity of the drug in the polymer respectively (Cp
is essentially equal to CR; where CR is the concentration of drug in the reservoir
compartment)
60

55. MICRORESERVOIR/MICRO SEALED
DISSOLUTION-CONTROLLED SYSTEM
This is a combination of reservoir
and matrix diffusion type drug
delivery system
In this system, the drug reservoir is
made by two steps
•Dispersion of solid drug particles in an
aqueous solution of water-soluble liquid
polymer
•Homogeneous dispersion or suspension
of drug in a lipophilic polymer by high
energy dispersion technique
As a result, numbers of separate,
microscopic spheres of drug
reservoirs are formed which do not
leach the drug
This is a thermodynamically
unstable system; hence requires
stabilization
It is stabilized by immediate in-situ
crosslinking the polymer chains
Thus, medicated polymer discs
having a definite or constant
surface area and of fixed thickness
are obtained
The device so obtained may be
further coated with a layer of
biocompatible polymer to modify
the rate of release of the drug
By placing the medicated disc at
the center and by surrounding disc
with an adhesive film, a TDDS is
produced
61

56. 62

57. 63
 Micro reservoir system can release the
drug following zero-order kinetics
without the chance of dose dumping.
 The rate of release of the drug from
this system can be expressed as:
Dl = Diffusivity of the drug in the liquid layer surrounding the
drug particle,
Dp = Diffusivity of drug in polymer coating membrane
surrounding polymer matrix,
Dd = Diffusivity of drug in the hydrodynamic diffusion layer
surrounding polymer coating with a respective thickness of hl,
hp, hd
Kl = Partition coefficient for the interfacial partitioning of the
drug from the liquid compartment to the polymer matrix,
Km = Partition coefficient for the interfacial partitioning of the
drug from the polymer matrix to the polymer coating
membrane,
Kp = Partition coefficient for the interfacial partitioning of the
drug from the polymer coating membrane to the elution
solution (skin),
Sl = Solubility of the drug in the liquid compartment,
Sp = Solubility of the drug in the polymer matrix,
Depending on the relative values of Sl and Sp the release of
drug from this system can follow either a partition control or
matrix diffusion-control process

58. EVALUATION OF TDDS
64

59. THICKNESS OFTHE 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
65

60. WEIGHT UNIFORMITY
 The prepared patches are to be dried at 60°C for 4 h before testing.
 A specified area of patch is to be cut in different parts of the patch and weighed in
a digital balance.
 The average weight and standard deviation values are to be calculated from the
individual weights
66

61. FOLDING ENDURANCE
 A strip of the specific area is to be cut evenly and repeatedly folded at the same
place till it breaks.
 The number of times the film can be folded at the same place without breaking
gives the value of the folding endurance
67

62. PERCENTAGE MOISTURE CONTENT
 The prepared films are to be weighed individually and are to be kept in a
desiccator containing fused calcium chloride at room temperature for 24 h.
 After 24 h, the films are to be reweighed to determine the percentage moisture
content from the below-mentioned formula:
% 𝑚𝑜𝑖𝑠𝑡𝑢𝑟𝑒 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 =
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡 − 𝑓𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝐹𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝑋100
68

63. PERCENTAGE MOISTURE UPTAKE
 The weighed films are to be kept in a desiccator at room temperature for 24 h,
which contains a saturated solution of potassium chloride in order to maintain
84% RH.
 After 24 h, the films are to be reweighed to determine the percentage moisture
uptake from the below-mentioned formula:
69
% 𝑚𝑜𝑖𝑠𝑡𝑢𝑟𝑒 𝑢𝑝𝑡𝑎𝑘𝑒 =
𝐹𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡 − 𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝑋100

64. WATERVAPOR PERMEABILITY
EVALUATION
 It can be determined with the foam dressing method, wherein the air-forced oven
is replaced by a natural air circulation oven.
 The WVP can be determined by the following formula:
𝑊𝑉𝑃 =
𝑊
𝐴
Where,
WVP is expressed in gm/m2 per 24 h
W = the amount of vapor permeated through the patch, expressed in gm/24 h
A = the surface area of the exposure samples, expressed in m2
70

65. DRUG CONTENT
 A specified area of the patch is to be dissolved in a suitable solvent in a specific
volume.
 Then, the solution is to be filtered through a filter medium and analyze the drug
content with the suitable method (UV or HPLC technique).
 Each value represents an average of three different samples
71

66. UNIFORMITY OF CONTENTTEST
 An accurately weighed portion of the patch is to be cut into small pieces and
transferred to a specific volume using a volumetric flask, dissolved in a suitable
solvent and sonicate for complete extraction of the drug from the patch and made
up to the mark with the same.
 The resulting solution is allowed to settle for about 1 h and the supernatant is
suitably diluted to give the desired concentration with the suitable solvent.
 The solution is filtered using a 0.2-µm membrane filter and analyzed by a suitable
analytical technique (UV or HPLC), and the drug content per piece is calculated
72

67. POLARISCOPE EXAMINATION
 This test is to be performed to examine the drug crystals from the patch by a
polariscope.
 A specific surface area of the piece is to be kept on the object slide and observed
for the drug crystals to distinguish whether the drug is present as a crystalline
form or an amorphous form in the patch.
73

68. SHEAR ADHESIONTEST
 This test is to be performed for measurement of the cohesive strength of an
adhesive polymer.
 It can be influenced by the molecular weight, the degree of crosslinking and the
composition of the polymer and the type and amount of tackifier added.
 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 taken for removal, greater is the shear strength
74

69. PEEL ADHESIONTEST
 In this test, the force required to remove an adhesive coating from a test substrate is referred to as peel
adhesion
 Molecular weight of the adhesive polymer and the type and amount of additives are the variables that
determine the peel adhesion properties.
 A single tape is applied to a stainless steel plate or a backing membrane of choice and then the tape is pulled
from the substrate at a 90º or 180º angle, and the force required for tape removal is measured
75

70. THUMBTACKTEST
 It is a qualitative test applied for tack property determination of the adhesive.
 The thumb is simply pressed on the adhesive and the relative tack property is
detected
76

71. FLATNESSTEST
 Three longitudinal strips are to be cut from each film at different portions, like one
from the center, one from the left side and another from the right side.
 The length of each strip is measured and the variation in length because of non-
uniformity in flatness is measured by determining the percent constriction, with
0% constriction equivalent to 100% flatness
% 𝑐𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 =
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑙𝑒𝑛𝑔𝑡ℎ −𝑓𝑖𝑛𝑎𝑙 𝑙𝑒𝑛𝑔𝑡ℎ
𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝐿𝑒𝑛𝑔𝑡ℎ
X100
77

72. PERCENTAGE ELONGATION BREAKTEST
 The percentage elongation break is to be determined by noting the length just
before the break point.
 The percentage elongation can be determined from the below-mentioned
formula:
78
% 𝑒𝑙𝑜𝑛𝑔𝑎𝑡𝑖𝑜𝑛 =
𝐹𝑖𝑛𝑎𝑙 𝑙𝑒𝑛𝑔𝑡ℎ − 𝐼𝑛𝑖𝑡𝑖𝑎𝑙 𝑙𝑒𝑛𝑔𝑡ℎ
𝐹𝑖𝑛𝑎𝑙 𝐿𝑒𝑛𝑔𝑡ℎ
X100

73. ROLLING BALLTACKTEST
 This test measures the softness of a polymer that relates to tack.
 In this test, a stainless steel ball of 7/16 inches in diameter is released on an
inclined track so that it rolls down and comes in contact with the horizontal,
upward facing adhesive.
 The distance the ball travels along the adhesive provides the measurement of
tack, which is expressed in inches
79

74. QUICK STICK (PEEL-TACK)TEST
 In this test, the tape is pulled away from the substrate at 90º at a speed of 12
inches/min.
 The peel force required to break the bond between the adhesive and the
substrate is measured and recorded as tack value, which is expressed in ounces or
grams per inch width
80

75. PROBETACKTEST
 In this test, the tip of a clean probe with a defined surface roughness is brought
into contact with the adhesive.
 And, when a bond is formed between the probe and the adhesive, the subsequent
removal of the probe mechanically breaks it.
 The force required to pull the probe away from the adhesive at a fixed rate is
recorded as tack, and it is expressed in grams
81

76. INVITRO DRUG RELEASE STUDIES
 The paddle over disc method (USP apparatusV) can be employed for assessment
of the release of the drug from the prepared patches.
 Dry films of known thickness are to be cut into a definite shape, weighed and
fixed over a glass plate with an adhesive.
 The glass plate is then placed in 500 mL of the dissolution medium or phosphate
buffer (pH 7.4), and the apparatus is equilibrated to 32 ± 0.5°C.
 The paddle was then set at a distance of 2.5 cm from the glass plate and operated
at a speed of 50 rpm.
 Samples (5 mL aliquots) can be withdrawn at appropriate time intervals up to the
predetermined time and analyzed by a UV spectrophotometer or HPLC.
82

77. INVITRO SKIN PERMEATION STUDIES
 An in vitro permeation study can be carried out by using diffusion cells.
 Full-thickness abdominal skin of maleWistar rats weighing 200–250 g is selected.
 Hair from the abdominal region is to be removed carefully by using a electric clipper; the dermal side of the skin
is thoroughly cleaned with distilled water to remove any adhering tissues or blood vessels, equilibrated for 1 h in
dissolution medium or phosphate buffer pH 7.4 before starting the experiment.
 The contents of the receptor chamber are mixed magnetically
 The temperature of the cell was maintained at 32 ± 0.5°C using a thermostatically controlled heater.
 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.
 Definite volume of sample is to be removed from the receptor compartment at regular intervals, and an equal
volume of fresh medium is to be replaced.
 Samples are to be filtered through the filtering medium, and can be analyzed spectrophotometrically or by using
HPLC.
 Flux can be determined directly as the slope of the curve between the steady state values of the amount of drug
permeated (mg/ cm2) versus time in hours, and permeability coefficients were deduced by dividing the flux by
the initial drug load (mg/cm2) 83

78. 84

79. SKIN IRRITATION STUDY
 Skin irritation and sensitization testing can be
performed on healthy rabbits (average weight
1.2–1.5 kg).
 The dorsal surface (50 cm2) of the rabbit is to be
cleaned and the hair is to be removed from the
clean dorsal surface by shaving.
 Clean the surface by using rectified spirit and,
then, the representative formulations can be
applied over the skin.
 The patch is to be removed after 24 h and the
skin is to be observed and classified into five
grades on the basis of the severity of the skin
injury
85

80. STABILITY STUDIES
 Done as per ICH guidelines
 Samples stored in 2 conditions:
 30°C/65% RH
 40°C/75% RH
 The samples are withdrawn at 0, 90, and 180 days
 The samples are evaluated for all relevant tests
86

81. MARKETED PRODUCTS
87

82. 88

83. 89