EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEMS

PRESENTED BY: GUIDED BY:
SANI SINGH Prof. VIKAS ANAND
M. Pharm (Pharmaceutics)
2nd Semester
EVALUATION OF TRANSDERMAL
DRUG DELIVERY SYSTEMS
SARDAR BHAGWAN SINGH P.G. INSTITUTE OF BIO-MEDICAL SCIENCES & RESEARCH,
BALAWALA, DEHRADUN, (UTTARAKHAND)
SECOND SEMINAR (MPHR 120)
2016-17

ORGANISATION
 Introduction
 Evaluation Methods
 Physicochemical Evaluation
 In-vitro Evaluation
 In-vivo Evaluation
 Marketed Products Available In India
 FDA Approved TDDS Products
 Recent Research Report From Pubmed

Transdermal drug delivery systems (TDDS, “Patch”) are self-contained, discrete dosage
forms that, when applied to intact skin, are designed to deliver the drug(s) through the skin
to the systemic circulation.
INTRODUCTION
IDEAL
SYSTEM
Agent
independent
Flexibility
Monitoring &
decision-
making
Targeting
 Vyas SP, Khar RK. Controlled drug delivery: Concepts and advances. 2nd edition. Vallabh Prakashan.
2012, 397-398.

Physicochemical evaluation
 Interaction studies
 Thickness of the patch
 Weight uniformity
 Drug content determination
 Content uniformity
 Folding endurance
 Flatness
 Moisture content
 Moisture uptake
 Water vapour permeability (WVP) evaluation
 Tensile strength
 Evaluation of adhesive
a) Shear adhesion test
b) Peel adhesion test
c) Tack properties
i. Thumb tack test
ii. Rolling ball test
iii. Quick stick (Peel tack test) test
iv. Probe tack test

Physicochemical evaluation
1. Interaction studies:
 Interaction studies ( drug and excipients ) are commonly carried out in Thermal analysis,
Fourier transform infrared spectroscopy (FTIR), UV and chromatographic techniques by
comparing their physicochemical characters such as assay, melting point, wave numbers,
absorption maxima etc.
2. Thickness of the patch: *
 The thickness of the drug loaded patch is measured in different points by using a digital
micrometer, dial gauge, screw gauge.
3. Weight uniformity: *
 The prepared patches are to be dried at 60°c for 4 hrs before testing. Individually
weighing 10 randomly selected patches a specified area of patch is to be cut in different parts
of the patch and weigh in digital balance.
Lembhe Swapnil, Dev Asish. Trasdermal Drug Delivery System: An Overview. World Journal Of
Pharmacy And Pharmaceutical Science. 2016;5(7): 584-610.
* Shinde et al. Recent Advances In Transdermal Drug Delivery System. Journal Of Pharmacy Research.
2012; 5(1):447-456.

4. Drug content determination: *
accurately weighed portion of film (about
100 mg) is dissolved in 100 ml of suitable
solvent & shaken continuously for 24 h,
then sonicated
After sonication and subsequent
filtration, drug in solution is estimated
spectrophotometrically
10 patches are selected, if 9 out of 10
patches have content between 85% to
115% and 1 has content not less than
75% to 125% of the specified value,
patches pass the test
3 patches range of 75% to 125%, then
additional 20 patches are tested . If
these 20 patches have range from 85%
to 115%, then the transdermal patches
pass the test.
5. Content uniformity test: *
2012; 5(1):447-456.

6. Folding endurance: #
7. Flatness test: *
 In flatness determination one strip is cut from the centre and two from each side of
patches. The length of each strip is measured and variation in length is measured by
determining percent constriction. 0 % constriction is equivalent to 100 % flatness.
% constriction = I1 – I2 X 100
I1
I1 = Initial length of each strip
I2 = Final length of each strip
Repeatedly
folding a small
strip of the patch
at the same place
till it broke.
The number of
times the patch
could be folded
at the same place
without breaking
Folding
endurance value
# Chauhan et al. Transdermal Patches: A Review On Novel Approach For Drug Delivery. Indo American
Journal Of Pharmaceutical Research.2015; 5(1):531-548.
2012; 5(1):447-456.

8. Percentage Moisture content:
 The weighed films are to be kept in a desiccator containing fused calcium chloride at
room temperature for 24 hrs. After 24 hrs the films are to be reweighed and determine the
percentage moisture content from the formula –
Percentage moisture content = [Initial weight - Final weight/ Final weight] ×100
9. Percentage Moisture uptake:
 The weighed films are to be kept in a desiccator containing saturated solution of
potassium chloride at room temperature for 24 hrs (84% RH). After 24 hrs the films are to be
reweighed and determine the percentage moisture uptake from the formula –
Percentage moisture uptake = [Final weight - Initial weight/ initial weight] ×100

10. Water vapour permeability (WVP) evaluation:
WVP=W/A
Where, WVP is expressed in gm/m2 per 24 hrs,
W is the amount of vapour permeated through the patch (gm/24 hrs)
A is the surface area of the exposure samples (m2)
Water vapour
permeability can be
determined by a natural
air circulation oven. The
WVP can be determined
by the following
formula:

weights are added to
the pan attached with
the hanging end of the
thread. A pointer is
used to measure the
elongation of the film.
The weight sufficient
to break the film is
noted.
One end is fixed
with the help of
an iron screen &
other end is
connected to a
freely movable
thread over a
pulley.
Polymeric films
are sandwiched
separately by
corked linear iron
plates
11. Tensile Strength: *
Tensile strength= F/a.b (1+L/l)
F is the force required to break;
a is width of film;
b is thickness of film;
L is length of film;
l is elongation of film at break
point.
* Shinde et al. Recent Advances In Transdermal Drug Delivery System. Journal Of Pharmacy
Research. 2012; 5(1):447-456.

12. Evaluation of adhesive:
a) Shear Adhesion test:
 Shear adhesion strength is determined by measuring (cohesive strength of an adhesive
polymer) the time it takes to pull the tape off the plate.
Shear strength test for adhesive evaluation
Jain NK. Controlled And Novel Drug Delivery. 1st edition. CBS Publishers & Distributors.1997,107-110.

b) Peel Adhesion test:
 In this test, the force required to remove an adhesive coating form a test substrate is
referred to as peel adhesion.
Peel adhesion test for adhesive evaluation

c) Tack properties:
 It is ability of a polymer to adhere to a substrate with little contact pressure. Test is includes.
 Thumb tack test:
 It is a qualitative test and the force required to remove thumb from adhesive is a measure of
tack.
Rolling ball tack test:
 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.
Rolling ball tack test for adhesive evaluation
T Himanshi, S Ruchika. Transdermal Drug Delivery System: A Review. International Journal Of
Pharmaceutical Sciences And Research. 2016;7(6): 2274-90.

 Quick Stick (peel-tack) test:
 The peel force required breaking the bond between an adhesive and substrate is measured by
pulling the tape away from the substrate at 90 at the speed of 12 inch/min.
Quick stick test for adhesive evaluation

 Probe Tack test:
 The tip of a clean probe is contact with adhesive and bond is formed between probe and
adhesive.
 The force required to pull the probe away from the adhesive at fixed rate is recorded as tack
and it is expressed in grams.
Probe tack test for adhesive evaluation
Probe
Force gauge

In-vitro drug release
studies
In-vitro skin
permeation studies
In – vitro evaluation

1. In vitro drug release studies: *
 A number of mathematical model is describe the drug dissolution kinetics from controlled
release drug delivery system e.g., Higuchi model, First order, Zero order and Peppas &
Korsenmeyer model.
 The dissolution data is fitted to these models and obtained the release mechanism of the
drug. There are various methods available for determination of drug release rate of TDDS.
In–vitro evaluation
Research. 2012; 5(1):447-456.

Higuchi model
Peppas &
Korsenmeyer model
A=[D (2C-Cs) Cs x t] ½
Where , A – amount of drug released in time
‘t’ per unit area
C – initial drug concentration
Cs – drug solubility in the matrix media
D – diffusivity of drug molecule in the matrix
substance
F = (Mt/M) = Km tn
Where, F – fraction of drug release at time ‘t’
Mt - amount of drug release at time ‘t’
M – total amount of drug in dosage form
Km - kinetic constant
n – diffusion or release exponent
t - time (hrs)

 Paddle over disc: * (USP apparatus 5)
 This method the transdermal system is attached to a disc or cell resting at the bottom of
the vessel which contains medium at 32 ±5°C.
Research. 2012; 5(1):447-456.

 Cylinder modified USP Basket: * (USP apparatus 6)
 This method is similar to the USP basket type dissolution apparatus, except that the
system is attached to the surface of a hollow cylinder immersed in medium at 32 ±5°C.
2012; 5(1):447-456.

 Reciprocating disc: * (USP apparatus 7)
 In this method patches attached to holders are oscillated in small volumes of medium,
allowing the apparatus to be useful for systems delivering low concentration of drug. In
addition paddle over extraction cell method may be used.
2012; 5(1):447-456.

2. In vitro skin permeation studies: *
 The transdermal system is applied to the hydrophilic side of the membrane (donor
compartment) and then mounted in the diffusion cell with lipophilic side in contact with
receptor fluid (receptor compartment, usually temprature 32±5°C for membrane ) in vertical
diffusion cell such as Franz diffusion cell or Keshary-chien (K-C) diffusion cell and is
continuously stirred at a constant rate.
 The samples are withdrawn at different time intervals and diluted appropriately then
absorbance is determined spectrophotometrically.
 Then the amount of drug permeated per cm2 at each time interval is calculated.
2012; 5(1):447-456.

Franz diffusion cell:

1. Animal models: #
 In-vivo animals models are preferred because considerable time and resources are
required to carry out studies in humans. Some of the species are used : mouse, rat, guinea
pig, rabbit, rat, cat, dog, pig, house, monkey small hairy animals (e.g. rat, rabbit) or rhesus
monkey is most reliable or in vivo evaluation of transdermal patches standard radiotracer
methodology used.
 The application site is generally the abdomen which are the least hairy site on the
animals body. The compound is applied after light clipper showing of the site.
In –vivo evaluation
# Chauhan et al. Transdermal Patches: A Review On Novel Approach For Drug Delivery. Indo
American Journal Of Pharmaceutical Research.2015; 5(1):531-548.

2. Human models: #
 It is first described by Fieldman and Maibach. They includes determination of
percutaneous absorption by an indirect method of measuring radioactivity in excreta
following topical application of the labeled drug. 14C is generally used for radio labeling.
 Determination of absorption of know amount of radioactivity retained in the body or
excreted by routes. The percentage of dose absorbed transdermally is then calculated as.
% Close absorbed = Total radioactivity exerted after topical Administration x 100
Total radioactivity exerted intervenes was Administration
The procedure takes 5-7 days for completion.
# Chauhan et al. Transdermal Patches: A Review On Novel Approach For Drug Delivery. Indo
American Journal Of Pharmaceutical Research.2015; 5(1):531-548.

(a) Reservoir
technique :
(b) Mass
balance
technique :
 It makes use of the relationship between stratum corneum
reservoir function and in vivo percutaneous absorption to
predict in vivo penetration.
 This method is involves a simple, short exposure of the skin
to the compound under study followed by removal of the
stratum corneum by tape stripping and analysis of the content
of the compound in the stratum corneum.
 The application site is covered with an occlusive chamber, the
chamber being replaced by a new one after a particular time
interval. The site is also subjected to washing at these time.
Radio labeling techniques are used and the chamber, washing
and the faces and urine of the patients are subjected to analysis.
 In this technique include achievement of mass balance
between the applied close and exertion level and measurement
for predicting percutaneous.

3. Biophysical Models:
 Models based on steady-state mass balance equation, solution of Fick’s second law of
diffusion for the device, stratum corneum and viable epidermis, as well as linear kinetics
have been described in the literature.
 It can be concluded that many techniques for in-vivo evaluation of transdermal systems
have been put forward there is scope for further refinement. Some of the unresolved issues
include the barrier function of the skin with age, skin metabolism, in-vivo functioning of
penetration enhancers etc.

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.
Regulatory requirements: *
 A transdermal patch is classified by U.S. Food and Drug Administration (FDA) as a
combination product, consisting of a medical device combined with drug or biologic product
that the device is designed to deliver. Prior to sale, any transdermal patch product must
receive approval from FDA, demonstrating safety and efficacy for its intended use.
Shinde Utkarsh P et al. Recent Advances In Transdermal Drug Delivery System. Journal Of Pharmacy
Research. 2012;5(1):447-456.
*

Marketed Products
Therapeutic
Agent
Brand Name Manufacturer Name Indication
Fentanyl Fendrop Sun Pharmaceutical
Industries Ltd
Moderate/severe pain
Rivastigmine Alzamine Bliss GVS Pharma
Limited
Dementia
Tulobuterol Astherol Bliss GVS Pharma
Limited
Anti-asthmatic
Fentanyl F- TAN Bliss GVS Pharma
Limited
Moderate/severe pain
Ketoprofen Ketopron Bliss GVS Pharma
Limited
Musculoskeleton pain
and Inflammation
Diclofenac
Diethylamine
Lofnac Bliss GVS Pharma
Limited
Musculoskeleton pain
and Inflammation

Therapeutic
Agent
Brand Name Manufacturer
Name
Indication
Fentanyl Fen-Touch Sparsha Pharma Moderate/severe pain
Ketoprofen Artho-Touch Sparsha Pharma Musculoskeleton pain
and Inflammation
Diclofenac Diclo-Touch Sparsha Pharma Musculoskeleton pain
and Inflammation
Rivastigmine Memory-Touch Sparsha Pharma Dementia

Therapeutic
Agent
Brand Name Manufacturer Name Indication
Diclofenac Nupatch Zydus Cadila
Healthcare Ltd.
Musculoskeleton
pain and
Inflammation
Fentanyl Finrid Dr. Reddy’s Moderate/severe pain
Fentanyl Trofentyl Troikaa Moderate/severe pain
Fentanyl Durogesic Johnson & Johnson Moderate/severe pain
http://www.drugsupdate.com/brand/brand_name/FENDROP
 http://www.blissgvs.com/products/pharma-products/transdermal-patches
http://sparsha.com/fen_touch.html
 http://sparsha.com/diclo_touch.html
 http://sparsha.com/artho_touch.html
http://sparsha.com/memory-touch.html
 http://www.drugsupdate.com/brand/brand_name/NUPATCH
 http://www.drugsupdate.com/brand/brand_name/FINRID
 http://www.drugsupdate.com/brand/brand_name/TROFENTYL
 http://www.drugsupdate.com/brand/brand_name/DUROGESIC

FDA Approved TDDS Products
Drug Name Generic Name Approval Date
CATAPRES TTS CLONIDINE October 10, 1984
VIVELLE ESTRADIOL October 28, 1994
CLIMARA ESTRADIOL December 22, 1984
ESTRADERM ESTRADIOL September 10, 1986
CLIMARA PRO ESTRADIOL/LEVONOR
GESTREL
November 21, 2003
ORTHO EVRA NORELGESTROMIN/ET
HINYL ESTRADIOL
November 20, 2001
DURAGESIC FENTANYL August 7, 1990

LIDOCAINE LIDOCAINE May 21, 1996
NITRO-DUR NITROGLYCERIN April 4, 1995
MINITRAN NITROGLYCERIN August 30, 1996
OXYTROL OXYBUTYNIN February 26, 2003
EXELON PATCH RIVASTIGMINE July 6, 2007
TRANSDERM-SCOP SCOPOLAMINE Approved prior to January
1, 1982
ANDRODERM TESTOSTERONE September 29, 1995

NICODERM NICOTINE August 2, 1996
HABITROL NICOTINE November 12, 1999
NICOTROL NICOTINE July 3, 1996
TRANSDERM-NITRO NITROGLYCERIN February 27, 1996
TESTODERM-AT TESTOSTERONE December 18, 1997
 Sadrieh Nakissa. Challenges in the Development of Transdermal Drug Delivery
Systems. Advisory Committee for Pharmaceutical Science and Clinical Pharmacology.
2009. (www.fda.gov)

Drug Polymer or
Major
Excipients
Type of Patch
and
Preparation
Method
Remarks Reference
IQP-0410
(HIV Inhibitor)
EC, HPMC, PG,
DnBP (Di-n-butyl
phthalate)
EC/HPMC-
based
transdermal films
& solvent casting
technique
Successful in vitro
reduction of HIV-1
activity from the
delivered drug over a
3 day application
suggests the potential
of IQP-0410 to be
administered via
transdermal patches.
Ham et al, 2013
Donepezil Sodium alginate
(matrix-forming
agent), Propylene
glycol and dl-
limonene
Matrix type
transdermal films
Alternative Delivery
Approach in
Alzheimer’s Disease
Treatment
Galipoglu et al,
2014

Drug Polymer or
Major
Excipients
Type of Patch
and
Preparation
Method
Remarks Reference
Buprenorphine Lauryl alcohol,
Tween 80,
Levulinic acid
(Chemical
penetration
enhancers)
Drug In Adhesive
Patch & Using
Box-Behnken
Experimental
Design
Chemical
penetration
enhancers could
enhance
permeation flux
of buprenorphine
through the skin
Taghizadeh et al,
2015
Zolmitriptan Oleic acid and
Span 80,
Isopropyl
myristate (IPM) ,
Triethylamine,
Azone
Drug in Adhesive
Patch & Solvent
evaporation
technique
Pharmacokinetic
parameters were
determined via
i.v. and
transdermal
administrations
using animal
model of rabbit.
Chao Liu and
Liang Fang, 2015

Drug Polymer or
Major
Excipients
Type of Patch
and
Preparation
Method
Remarks Reference
Khardal
(Brassica nigra),
Zanjabeel
(Zingiber
officinale),
Podina (Mentha
arvensis)
Chitosan,
PEG-400,
tween 80
Drug in Adhesive
Patch & solvent
evaporation
technique
Design and development
of an antiemetic
transdermal Unani
formulation in a novel
dosage form for a common
clinical condition, namely,
vomiting/emesis. The patch
was found to be stable &
showed no signs of skin
irritation.
Saleem M
N & Idris
M, 2016
Galipoglu et al. Biopolymer-Based Transdermal Films of Donepezil in Alzheimer’s. AAPS Pharm Sci Tech
2014; 16(2): 284-292.
Taghizadeh et al. Influence of skin penetration enhancers on buprenorphine patch release system. Journal of
Advanced Research . 2015; 6: 155–162.
 Chao Liu and Liang Fang. Transdermal Patch of Zolmitriptan and Pharmacokinetic Study. AAPS Pharm
SciTech. 2015; 16 (6): 1245-1253.
 Ham et al. IQP-0410 HIV Inhibitor Transdermal Film. PLOS ONE. 2013; 8(9): e 75306.
 Saleem MN, Idris M. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic
Therapy and Its Pharmaceutical Evaluation. [P.G. Unani Thesis]. Ayurvedic & Unani Tibbia College, Karol
Bagh, New Delhi, India, 2016.

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