Snehal transdermal delivery system

UNIVERSITY SEMINAAR ON
TRANSDERMAL DRUG
DELIVERY SYSTEM
Guided by
Dr. P.R.Mahaparle,
H.O.D Dept. of Pharmaceutics,
Padm. Dr. D. Y. Patil College of Pharmacy,Akurdi
By,
NAME- Miss. SNEHAL K. DHOBALE
Class- M-PHARMACY – 2nd semester : Dept. of
Pharmaceutics
College- Padm. Dr. D.Y.PATIL COLLEGE OF
PHARMACY, AKURDI

CONTENTS
• INTRODUCTION
• ADVANTAGES
• DISADVANTAGES
• ANATOMY OF HUMAN SKIN
• PATHWAYS OF DRUG PENETRATION
• COMPONENTS OF TRANSDERMAL DRUG DELIVERY
SYSTEM
• TYPES OF TDDS
• APPROACHES TO TDDS
• SALES OF TDDS
• MARKETED PREPARATIONS
• EVALUATION
• RECENT ADVANCES
• CONCLUSION
• REFERENCES 2

INTRODUCTION
 Transdermal drug delivery is the delivery of drugs
through the skin to elicit a systemic effect.
 It delivers a drug through intact skin at a controlled
rate into the systemic circulation.
 The passage of substance from the outside of the
skin through its various layers into the bloodstream
 Transdermal delivery represents an attractive
alternative to oral delivery of drugs
 It provides an alternative to hypodermic injection
too.
3

ADVANTAGES
Avoidance of first pass metabolism
Avoidance of gastro intestinal incompatibility
Minimizing undesirable side effects
Avoiding the fluctuation in drug levels
Maintain plasma concentration of potent drugs
Termination of therapy is easy at any point of time
Greater patient compliance due to elimination of multiple dosing profile
Ability to deliver drug more selectively to a specific site
Provide suitability for self administration
Enhance therapeutic efficacy
4

DISADVANTAGES
5
It is limited only to potent drug molecule.
Drugs with short biological half life that are subject to large first pass
metabolism.
Drugs must not be locally irritating or sensitizing.
Drug that require high blood levels cannot be administered
Adhesive may not adhere well to all types of skin
Drug or drug formulation may cause skin irritation or sensitization
Uncomfortable to wear
May not be economical

6
ANATOMY OF SKIN
Skin is a multilayered organ
It is composed of three tissue layers mainly
EPIDERMIS
• Outer layer of the skin
• Composed of stratified squamous epithelial cells.
• These are held together mainly by highly convoluted interlocking
bridges which are responsible for the unique integrity of skin .
DERMIS
• It is composed of network of collagen & elastic fibers embedded in a
mucopolysaccharide matrix, which contain blood vessels, lymphatic &
nerve endings, thereby providing physiological support for
epidermis
SUBCUTANEOUS TISSUE
• This is a sheet of fat containing areolar tissue, known as superficial
fascia, attaching the dermis to underlying structure

7
Routes of penetrations
1.Through stratum corneum
2.Transfollicular
3.Through sweat gland
MECHANISM OF ABSORPTION

KINETICS OF TRANSDERMAL
PERMEATION
• Percutaneous absorption of most drugs is a passive
diffusion process that can be described by Ficks’s first
law of diffusion
dQ/dt=JT A ΔC
• JT is the total flux transported through a unit area of
skin per unit time in steady state (µg/hr)
• A is the area of skin
• P is the effective permeability of skin
• ΔC is the drug concentration gradient across the skin

Drug
• Should possess an
adequate solubility in oil
and water.
• Should have a molecular
weight less than
approximately 1000
daltons.
• Require a balanced
partition coefficient to
penetrate in the stratum
corneum.
• Should have low melting
point.
Polymer matrix
• They are matrices that
regulate the release of
the drug
• Natural polymers: shellac,
gelatin, waxes, gums,
starch etc.
• Synthetic polymers:
polyvinyl alcohol,
polyamide, polyethylene,
polypropylene, Polyurea,
polymethyl methacrylate.
BASIC COMPONENTS OF
TRANSDERMAL DDS

BASIC COMPONENTS OF
TRANSDERMAL DDS
Permeation
enhancer
• Substances which
temporarily
diminish the
impermeability of
the skin are known
as accelarants.
• These include
water, pyrolidones,
fatty acids and
alcohols, azone and
its derivatives,
alcohols and
glycols, essential
oils, terpenes
Adhesive
• Serves to adhere the
patch to the skin for
systemic drug
delivery of the drug
• Ex: Silicones,
Polyisobutylene
• Should not cause
irritation,
sensitization &
imbalance to skin
• Should adhere to
skin strongly
• Should be easily
removable.
• Should have intimate
contact with the
skin.
Backing layer
• Backing layer
protects patch from
outer environment
• Function of holding
the entire system
and protects drug
reservoir from
atmosphere.
• Should be
impermeable to drug
and penetration
enhancers.
• Ex: Cellulose
derivatives,
Polypropylene silicon
rubber

Membrane moderated
• The drug reservoir is
encapsulated in a
shallow compartment
moulded from a drug
impermeable metallic –
plastic lamination
• The drug molecules are
released only through
the rate controlling
membrane.
Adhesive diffusion controlled
• It is prepared by directly
dispensing the drug in an
adhesive polymer
• Then spreading the
medicated adhesive by
solvent film casting
method over a flat sheet
of drug impermeable to
plastic backing.
TYPES OF TDDS

TYPES OF TDDS
Matrix dispersion type
• It is formed by dispersing the
drug in a mixture of
hydrophilic – Lipophilic
polymer{matrix} & the
medicated polymer is
moulded on medicated disc
of defined surface area &
thickness .
• It is then glued over
occlusive base plate consisted
of compartment fabricated
using an impermeable plastic
backing
Micro reservoir type
• It has features of both
reservoir & matrix
dispersion type drug
delivery system.
• The drug reservoir is
formed by suspending the
drug solid in an aq. Solution
of water soluble polymer.
• The drug suspension is
dispersed homogenously

SALE OF DIFFERENT TDDS
13
Till 2012

MARKETED PREPARATIONS
Sr.
n
O
PRODUCT ACTIVE
DRUG
TYPE OF TD
PATCH
USE
1. Estraderm Estradiol Membrane Postmenstrual
syndrome
2. Duragesic Fentanyl Reservoir Pain relief patch
3. Alora Estradiol Matrix Postmenstrual
Syndrome
4. Androderm Testosterone Membrane Hypogonadism in males
5. Captopress
TTS
Clonidine Membrane Hypertension
6. Esclim Estradiol Matrix Harmone replacement
therapy
7. Deponit Nitroglycerine Drug in adhesive Angina Pectoris
8. Lidoderm Lidocaine Drug in adhesive Anesthetic 14

EVALUATION OF TDDS
Interaction studies
Peel Adhesion test
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
Flatness test
Percentage Elongation break test
Rolling ball tack test
Quick Stick (peel-tack) test
Skin Irritation study
In vitro drug release studies
In vitro skin permeation studies
Stability studies:
15

PEELADHESION TEST
In this test, the force
required to remove
an adhesive coating
form a test substrate
is referred to as peel
adhesion.
A single tape is applied
to a stainless steel
plate or a backing
membrane and then
tape is pulled from the
substrate at a 180º
angle.
16

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 weigh in digital balance
The average weight and standard deviation values are to
be calculated from the individual weights.
17

THICKNESS of PATCH
The thickness of the drug loaded patch is
measured in different points by using a digital
micrometer
It determines the average thickness and
standard deviation for the same to ensure
the thickness of the prepared patch.

PERCENTAGE MOISTURE
CONTENT
The prepared
films are
weighed
individually and
kept in a
desiccator
containing fused
calcium chloride
at RT for 24 hrs.
After 24 hrs the
films are
reweighed and
determine the
percentage
moisture
content from
mentioned
formula.
Percentage moisture content =
Initial weight− Final weight
Final weight]
× 𝟏𝟎𝟎
19
PERCENTAGE MOISTURE UPTAKE
The weighed films
are to be 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.
Percentage moisture uptake =
[Final weight− Initial weight]
𝐢𝐧𝐢𝐭𝐢𝐚𝐥 𝐰𝐞𝐢𝐠𝐡𝐭
×100

DRUG CONTENT
Then the solution is to be filtered through a filter
medium and analyse the drug content with the
suitable method (UV or HPLC technique).
A specified area of patch is to be dissolved in a
suitable solvent in specific volume.
20

UNIFORMITY OF DOSAGE
UNIT
An accurately weighed portion of the patch is to be
cut into small pieces a
transferred to a specific volumetric flask,
Then dissolved in a suitable solvent and
sonicate for complete extraction of drug from the
patch.
The resulting solution was allowed to settle for
about an hour and uniformity of dosage is measured
21

SHEAR ADHESION TEST
The longer the time take for removal, greater is the shear strength.
Shear adhesion strength is determined by measuring the time it takes to pull
the tape off the plate.
a specified weight is hung from the tape, to affect it pulling in a direction
parallel to the plate.
An adhesive coated tape is applied onto a stainless steel plate
22

FLATNESS TEST
Three longitudinal strips are to be cut from
each film at different portion like one from the
center, other one from the left side, and
another one from the right side.
The length of each strip was measured and the
variation in length because of non-uniformity in
flatness was measured by determining percent
constriction.
23

PERCENTAGE ELONGATION
BREAK TEST
• The percentage elongation break is to be
determined by the length before the break
point, the percentage elongation can be
determined from the below mentioned
formula.
• L1- final length of each strip
• L2- initial length of each strip
Elongation percentage =
(L 1 −L 2)
L 2
×100
24

ROLLING BALL TACK
TEST
This test measures
the softness of a
polymer.
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.
The distance the ball
travels along the
adhesive provides the
measurement of tack,
which is expressed in
inch.
25

QUICK STICK TEST
In this test, the tape is pulled away from
the substrate at 90ºC at a speed of 12
inches/min.
The peel force required to break the
bond between adhesive and substrate
is measured and recorded as tack value,
which is expressed in ounces or grams
per inch width.
26

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 (50cm 2 ) of the rabbit is to be cleaned
and remove the hair from the clean dorsal surface by
shaving and clean the surface by using rectified spirit and
the formulations can be applied over the skin.
The patch is to be removed after 24 hr and the skin is to be
observed and classified into 5 grades on the basis of the
severity of skin injury.
27

IN VITRO DRUG RELEASE
STUDY
The experiment is to be performed in triplicate and the mean value can be calculated.
Samples (5- ml aliquots) can be withdrawn at appropriate time intervals up to 24 h and
analyzed by UV spectrophotometer or HPLC.
The paddle was then set at a distance of 2.5 cm from the glass plate and operated at a
speed of 50 rpm.
The glass plate was then placed in a 500-ml of the dissolution medium or phosphate
buffer (pH 7.4), and the apparatus was equilibrated to 32± 0.5°C.
Dry films of known thickness is to be cut into definite shape, weighed, and fixed over a
glass plate with an adhesive.
The paddle over disc method (USP apparatus V) can be employed for assessment of the
release of the drug from the prepared patches.
28

In-Vivo drug release study
The release and skin permeation studies of drug can be
carried out by individually mounting a skin specimen
excised from either human cadaver or a live animal
(guinea pig or rabbbit) on a vertical diffusion cell such as
franz diffusion or horizontal diffusion cell such as Valia
chein skin permeation cell
Valia chein skin permeation cell
Franz diffusion

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 analyze suitably
for the drug content.
30

Microneedles TDDS (by-passing
SC)
• Microneedle array consists of chips, containing 300-
400 needles.
• Biocompatible materials required.
• Needle should be at least 20 µm in length to cross
the stratum corneum barrier.
• Used for adminstration of therapeutic proteins and
vaccines.

MICRONEEDLES FOR SKIN
PENETRATION
Direct and controlled delivery
Ability to manipulate drug
formulation; suspension, powder
Patient self-administration &Precise
control of penetration
Effortless and painless
Why Microneedle
Array?

Electroporation
Electroporation is increase in the electrical
conductivity and permeability of the cell
plasma membrane caused by an externally
applied electrical field.
It involves the application of short
(microsecond or millisecond), high voltage
(50-1000 volts) pulses to the skin.
The mechanism of penetration is the formation
of transient pores due to electric pulses that
subsequently allow the passage of
macromolecules from the outside of the cell to
the intracellular space.

Iontophoresis
Iontophoresis is a process of transportation of ionic
molecules into the tissues by passage of electric current
through the electrolyte solution containing the ionic
molecules using suitable electrodes.
Electrical energy assists the movement of ions across the
stratum corneum according to the basic electrical
principle of like charges repel each other and opposite
charges attracts.
The drug is applied under an electrode of the same
charge as the drug, and a return electrode opposite in
charge to the drug is placed at a neutral site on the body
surface.

ADVANCES IN TDDS
• Abstract
• A critical analysis of (trans) dermal delivery of substances encapsulated
within liposomes and niosomes is presented.
• Topical liposomes or niosomes may serve as solubilization matrix, as a
local depot for sustained release of dermally active compounds, as
penetration enhancers, or as rate-limiting membrane barrier for the
modulation of systemic absorption of drugs.
• The mechanism(s) of vesicle-skin interaction and drug delivery are being
extensively investigated using radioactive- or fluorescence-labeled
marker molecules and drugs, and various electron and (laser) light
microscopic visualization techniques, and different models describing
the interaction with and fate of vesicles in the skin have been proposed.
• The delivery of liposome-encapsulated proteins and enzymes into
deeper skin layers has been reported, although the mechanism of
delivery remains to be elucidated..
Liposomes and niosomes as topical drug carriers: dermal and transdermal drug
delivery
Hans Schreiera, Joke Bouwstrab

CONCLUSION
• Transdermal drug delivery system has been
recognized as a potential delivery system in
spite of its limitation.
• Essentially this drug delivery system brings
rate controlled delivery with fewer side effects
increased efficacy and constant delivery.
• The skin has an extremely good barrier
function and to improve the penetration of
active ingredients it is frequently necessary to
employ enhancement strategies.
36

REFERENCES
1) Brahmankar D. M., JaiswalS. B, (2004) Biopharmaceutics
and pharmacokinetics, Vallabh prakashan, Delhi, pp.337.
2) Chein.Y.W.,Novel Drug Delivery Systems, Marcel Dekker
series; Vol.50: second edition, pp.301-375.
3) Jain, N. K.,1981.Controlled and novel drug delivery, CBS
Publishers, New Delhi.pp.100-126.
4) Vyas S. P. Theory and practice in novel drug delivery
system, page no- 90.
5) Robinson J.R, Lee Vincent H. L controlled drug delivery,
fundamentals and application, second edition, volume-
20, page no- 523.
6) Donald L. Wise, Handbook of pharmaceutical controlled
release technology, page no- 445-452, 567-571.
7) International journal of biopharmaceutical and
toxicological research, volume -1, issue-1, May-2011.

Snehal transdermal delivery system

Snehal transdermal delivery system

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