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Transdermal drug delivery system with formulation and evaluation aspects:
Overview
Article  in  Research Journal of Pharmacy and Technology · January 2012
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Research J. Pharm. and Tech. 5(9): September 2012 
 
 1168
 
 
ISSN 0974-3618 www.rjptonline.org 
 
REVIEW ARTICLE 
 
Transdermal Drug Delivery System with Formulation and Evaluation 
Aspects: Overview 
Bhairam Monika*, Roy Amit, Bahadur Sanjib, Banafar Alisha, Patel Mihir, 
Turkane Dhanushram 
Columbia Institute of Pharmacy, Raipur. Chhattisgarh 
*Corresponding Author E-mail: monikab430@gmail.com 
 
 
ABSTRACT: 
Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery 
and differs from traditional topical drug delivery. The conventional oral dosage forms has significant drawbacks of 
poor bioavailability due to hepatic first pass metabolism and tendency to produce major fraction of drug is transported 
into the systemic blood circulation, leading to a need for high or frequent dosing, which can be both cost prohibitive 
and inconvenient. To improve such characters transdermal drug delivery system (TDDS) was emerged which will 
improve the therapeutic efficacy and safety of drugs by more precise (i.e. site specific) placement within the body 
thereby reducing both the size and number of doses. Today number of drugs is taken orally and is found not to be as 
effective as desired. To improve such characters transdermal drug delivery system was emerged. This article provides 
an overview on introduction about the transdermal drug delivery system and types of Transdermal patches, use of 
polymer as a transdermal drug delivery system, methods of preparation, and its physicochemical methods of evaluation 
and the types of transdermal systems currently available in the market to focus on the recent innovations in 
Transdermal Drug Delivery Systems which can be a platform for the research and development of pharmaceutical drug 
dosage form for Transdermal Drug Delivery. 
 
KEY WORDS: Transdermal drug delivery system (TDDS), Systemic blood circulation, Hepatic first pass 
metabolism,Skin permeation, Approaches. 
 
INTRODUCTION: 
Transdermal drug delivery systems (TDDS), also known as 
“patches,” are dosage forms designed to deliver a 
therapeutically effective amount of drug across a patient’s 
skin.
1
Transdermal drug delivery system has been in 
existence for a long time. In the past, the most commonly 
applied systems were topically applied creams and 
ointments for dermatological disorders. The occurrence of 
systemic side-effects with some of these formulations is 
indicative of absorption through the skin. A number of 
drugs have been applied to the skin for systemic treatment. 
In a broad sense, the term transdermal delivery system 
includes all topically administered drug formulations 
intended to deliver the active ingredient into the general 
circulation. Transdermal therapeutic systems have been 
designed to provide controlled continuous delivery of drugs 
via the skin to the systemic circulation.
2 
 
 
 
 
Received on 03.07.2012 Modified on 14.07.2012 
Accepted on 29.07.2012 © RJPT All right reserved 
Research J. Pharm. and Tech. 5(9): September 2012; Page 1168-1176 
 
Transdermal delivery not only provides controlled, constant 
administration of the drug, but also allows continuous input 
of drugs with short biological half-lives and eliminates 
pulsed entry into systemic circulation, which often causes 
undesirable side effects. Thus various forms of Novel drug 
delivery system such as Transdermal drug delivery systems, 
Controlled release systems, Transmucosal delivery systems 
etc. emerged. Several important advantages of transdermal 
drug delivery are limitation of hepatic first pass 
metabolism, enhancement of therapeutic efficiency and 
maintenance of steady plasma level of the drug. The first 
Transdermal system, Transderm -SCOP was approved by 
FDA in 1979 for the prevention of nausea and vomiting 
associated with travel, particularly by sea. The evidence of 
percutaneous drug absorption may be found through 
measurable blood levels of the drug, detectable excretion ofthe drug and its metabolites in the urine and through the 
clinical response of the patient to the administered drug 
therapy. 
3
 
 
Route of Penetration 
In order to design a successful transdermal drug delivery 
system (TDDS), it is important to understand the structure, 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1169
physiology and function of the skin. The skin is the largest 
organ and is primarily composed of three layers. The skin is 
divided into epidermis, dermis, and subcutaneous layer or 
hypodermis. Each layer has its own function and own 
importance in maintaining the integrity of skin and thereby 
the whole body structure. In the past, the most commonly 
applied systems were topically applied creams and 
ointments for dermatological disorders and these show local 
action but occurrence of systemic side-effects with some of 
these formulations is indicative of absorption through the 
skin this concept lead to the birth of TDDS.
4
 In a broad 
sense, the term transdermal delivery system includes all 
topically administered drug formulations intended to deliver 
the active ingredient into the general circulation. 
Transdermal therapeutic systems have been designed to 
provide controlled continuous delivery of drugs via the skin 
to the systemic circulation. Moreover, it over comes various 
side effects like painful delivery of the drugs and the first 
pass metabolism of the drug occurred by other means of 
drug delivery systems. TDDS has been a great field of 
interest in recent times. Many drugs which can be injected 
directly into the blood stream via skin have been formulated 
by TDDS.
4,5,6 
Penetration of the drug through the various 
layer of skin has shown in figure 1.
7 
 
Figure 1- Permeation Through Skin7 
 
Factors Affecting Transdermal Permeation 
 
Physicochemical properties of the penetrate molecules 
Partition coefficient, pH conditions, Penetrate 
concentration.
6,8 
 
Formulation factor 
� Physical chemistry of transport. 
� Vehicles and membrane used. 
� Penetration enhancers used. 
� Method of application. 
� Device used. 
 
Physiological factors 
� Stratum corneum layer of the skin. 
� Anatomic site of application on the body. 
� Skin condition and disease. Age of the patient. 
� Skin metabolism. Desquamation (peeling or 
flaking of the surface of skin ). 
� Skin irritation and sensitization. 
� race.6,9,10,11 
Advantages of Transdermal Drug Delivery Systems 
Delivery via the transdermal route is an interesting option 
because transdermal route is convenient and safe. The 
positive features of delivery drugs across the skin to achieve 
systemic effects are: 
� Avoidance of first pass metabolism. 
� Avoidance of gastro intestinal incompatibility. 
� Predictable and extended duration of activity. 
� Minimizing undesirable side effects. 
� Provides utilization of drugs with short biological half 
lives, narrow therapeutic window. 
� Enhance therapeutic efficacy.8 
� Drug administration stops with patch removal. 
� Alternate route for patients who are unable to take oral 
medications.
12
 
� Improved patient compliance and comfort via non-
invasive, painless and simple application.
13
 
 
Disadvantages of Transdermal Drug Delivery Systems 
� Only small, lipophilic drugs can be delivered currently 
through. 
� Drug molecule must be potent because patch size 
limits amount. 
� Drugs with very low or high partition coefficient fail to 
reach blood circulation.
12
 
� Easy elimination of drug delivery in case of toxicity. 
� Drugs that are highly melting can be given by this 
route due to their low solubility both in water and fat.
14
 
� Erythema, itching, and local edema can be caused by 
the drug, the adhesive, or other excipients in the patch 
formulation.
 6, 13, 15,16
 
 
Components of Transdermal Drug Delivery System 
DRUG 
Drug is in direct contact with release liner. The selection of 
drug for TDDS is based on physicochemical properties of 
drug. Transdermal drug delivery system is much suitable 
for drug having 
 
Physicochemical properties 
� The drug should have some degree of solubility in both 
oil and water (ideally greater than 1 mg/ml). 
� The substance should have melting point less than 
200°F. 
� Hydrogen bonding groups should be less than 2.8 
� Low molecular weight (less than 500 Daltons).17 
 
Biological properties 
� Drug should be very potent, i.e., It should be effective 
in few mg per day (ideally less than 25 mg/day). 
� Tolerance to drug must not develop under near zero 
order release profile of transdermal delivery. 
� The drug should not get irreversibly bound in the 
subcutaneous tissue. 
� The drug should not get extensively metabolized in the 
skin
8
 
� Narrow therapeutic window.17 
 
POLYMER MATRIX / DRUG RESERVOIR 
The polymers used for TDDS can be classified as: 
 
Natural polymers: e.g. cellulose derivatives, zein, gelatine, 
starch and chitosan ,etc. 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1170
Synthetic elastomers: e.g. polybutadiene, hydrin rubber, 
polyisobutylene, silicon rubber, nitrile, butylrubber etc. 
 
Synthetic polymers: e.g. polyvinyl alcohol, 
polyvinylchloride, polyethylene, polypropylene, epoxy, 
polyacrylate, polyamide, polyurea, polyvinylpyrrolidone, 
polymethylmethacrylate, hydroxypropylcellulose etc.
18,19
 
List of polymer given in table 1. 
 
Table 1: List of Polymers used in Transdermal Drug Delivery System20 
Polymer Type of System 
EthylCellulose T-50 Matrix 
BIO PSA Adhesive in Matrix 
Scotch Pak Backing/Release Liner 
Eudragit Matrix 
MDX -4-421 (a silicone) Matrix 
Acrylic PSA emulsion Drug-in-adhesive 
Acrylic adhesives Drug-in-adhesive 
Polyisobutylene solutions(Vistanex 
LM-MH, Vistanex MML-100) 
Drug-in-adhesive 
Silicone PSA Drug-in-adhesive 
Silicone Oil Resevoir 
EVA Membrane 
Polyisobutylene Adhesive 
ScotchPak 1006 Backing Film 
2-Ethylhexyl acrylate Drug-in-adhesive 
Acrylic acid copolymer Matrix 
PIB Matrix 
MDX4-4210 silicone elastomer Matrix 
Acrylate copolymer (Gelva-737) Matrix 
Silicone-2920 and 2675 Matrix 
2-Ethylhexyl acrylate and acrylic acid 
copolymer 
Drug-in-adhesive 
 
PERMEATION ENHANCERS 
The penetration enhancer should be pharmacologically 
inert, non toxic, non allergenic, non-irritating and ability to 
act specifically, reversibly and for predictable duration. It 
should not cause loss of body fluids, electrolytes or other 
endogeneous materials.
17, 21 
List of penetration enhancers 
given in table 2. 
 
PRESSURE SENSITIVE ADHESIVE (PSA) 
The pressure-sensitive adhesive (PSA) affixes the 
Transdermal drug delivery system firmly to the skin. It 
should adhere with not more than applied finger pressure, 
be aggressively and permanently tachy and exert a strong 
holding force. 
17.23 
 
The fastening of all transdermal devices to the skin has so 
far been done by using a pressure sensitive adhesive which 
can be positioned on the face of the device or in the back of 
the device and extending peripherally. 
 
The three major classes of polymers evaluated for potential 
medical applications in TDDS include: 
� Polyisobutylene type pressure sensitive adhesives. 
� Acrylic type pressure sensitive adhesives. 
� Silicone type pressure sensitive adhesives .8,17.23,24 
 
BACKING LAMINATES 
Backing materials must be flexible while possessing good 
tensile strength.
13
While designing a backing layer, the 
consideration of chemical resistance of the material is most 
important.
20
 List of baking membranes given in table 3. 
Examples of some backing materials are vinyl, 
polyethylene and polyester films.
15, 20 
 
RELEASE LINER 
Protects the patch during storage. The liner should be 
removed before its use.
14
The release liner has to be 
removed before the application of transdermal system, and 
it prevents the loss of the drug that has migrated into the 
adhesivelayer during storage. It also helps to prevent 
contamination. It is composed of a base layer, which may 
be non-occlusive (e.g. paper fabric) or occlusive(e.g. 
polyethylene, polyvinylchloride), and a release coating 
layer made of silicon or Teflon. Other materials include 
polyesters, foil, Mylar and metallized laminate
8. 
 
 
Table 2: Types of chemical classes that act as penetration 
enhancers.18.22 
CLASSES EXAMPLES 
Alcohols Alkanol: ethanol, propanol, butanol, pentanol, 
hexanol, octanol, Fatty alcohol: caprylic, decyl, 
lauryl, stearyl 
Alkanones N-heptane, N-octane, N-nonane, N-decane, N-
undecane 
Amides Cyclic amide: 1-dodecylazacycloheptane-2-one 
(Azone) Pyrrolidone derivate: 1-methyl-2-
pyrrolidone 
Urea, dimethylacetamide, diethyltoluamide, 
dimethylformamide 
Fatty acids Linear: heptanoic, lauric, myristic, oleic, stearic, 
valeric Branched: isovaleric, isostearic, 
neoheptanoic, neopentanoic 
Fatty acid 
esters 
Alkyl: butyl acetate, ethyl acetate, ethyl oleate, 
methylvalerate Aliphatic-isopropyl n-butyrate, 
isopropyl n-decanoate 
Organic acids Citric and succinic acid, salicylic acid and 
salicylates 
Polyols Butanediol, glycerol, hexanetriol, propylene 
glycol 
Sulfoxides Decylmethylsulfoxide, dimethylsulfoxide 
Surfactants Anionic: sodium laurate, sodium lauryl sulfate 
Cationic: benzalkonium chloride, cetyltrimethyl 
ammonium bromide, 
tetradecyltrimethylammonium bromide 
Nonionic: polyoxyethylene alkyl ethers, 
poloxamers, 
polysorbates. Bile salts: sodium cholate, 
glycholic 
Terpenes Alcohols: a-terpineol, carvol, terpinene-4-ol 
Hydrocarbons: a-pinene, b-carene, D-limonene 
Ketones: carvone, menthone, piperitone, 
pulegone 
Oils: anise, chenopodium, eucalyptus, ylang 
ylang 
Oxides: 1,8-cineole, cyclohexene oxide, limonene 
oxide 
 
The material properties to be considered for a release liner 
are as follows: 
� The material must be chemically inert. 
� The material should be such that it should not permeate 
the drug. 
� Affinity towards water should be null. 
� Material should not crack, craze, or react in any way 
with the mechanism that are used for penetration in 
active transdermal drug delivery systems.
20 
 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1171
Table 3: Characteristic of some commercialized baking membranes.20 
Product Polymer Oxygen Transmission 
(cm3/m2/24 h) 
MVTR 
(g/m2/24h) 
Enhancer Resistance 
CoTran 9701 Polyurethane Film 700 Low 
CoTran 9702, 
CoTran 9706 
EVA 52.8 
26.4 
Medium 
Medium 
CoTran 9720, 
9722 
PE 2950 
3570 
9.4 
7.9 
Medium 
High 
Foam Tape 9772L PVC foam 450 - 
Foam Tape 9773 Polyolefin foam - - 
Scotchpak 1006 PE, Al vapor coat, PET, EVA 4.6 0.3 High–PET side 
Scotchpak 1109 PE, Al vapor coat, PET 4.6 0.3 High 
Scotchpak 9723 PE, PET laminate 100 12 High 
Scotchpak 9732,9733 PET, EVA laminate 80 
80 
15.5 
17 
High–PET side 
High–PET side 
 
Other Excipients Like Plasticizers And Solvents 
Various solvents such as chloroform, methanol, acetone, 
isopropanol and dichloromethane are used to prepare drug 
reservoir. Plasticizers have been known to reduce the 
stiffness of the polymer backbone, thereby increasing the 
diffusion characteristics of the drug.
8 
In addition plasticizers 
such as dibutylpthalate , triethylcitrate, polyethylene glycol 
and propylene glycol are added to provide plasticity to the 
transdermal patch.
17,18, 25 
 
Types of Transdermal Patch Single Layer Drug In 
Adhesive 
 
Figure 2: Single-layer drug-in-adhesive24 
 
In this type the adhesive layer contains the drug.
8
 In this, 
the drug reservoir is totally encapsulated in a shallow 
compartment molded from a drug impermeable metallic 
plastic laminate and a rate controlling polymeric membrane. 
In the drug reservoir compartment, the drug solids are either 
dispersed in a solid polymer matrix or suspended in an 
unleachable, viscous liquid medium e.g. silicon fluid. The 
rate controlling membrane can be micro porous or 
nonporous polymeric membrane e.g. ethylene vinyl acetate 
co‐polymer on the external surface of the polymeric 
membrane, a skin layer of drug, compatible hypo allergic 
adhesive polymer may be applied to achieve an intimate 
contact of TDDS with skin surface.
6 
Single layer drug in 
adhesive type transdermal patch has shown in figure 2.
24 
 
Multi-Layer Drug-In-Adhesive 
The Multi-layer Drug-in-Adhesive is similar to the Single-
layer Drug-in-Adhesive in that the drug is incorporated 
directly into the adhesive. However, the multi-layer 
encompasses either the addition of a membrane between 
two distinct drug-in-adhesive layers or the addition of 
multiple drug-in-adhesive layers under a single backing 
film.
24, 26 
Patch assembly shown in figure 3.
24
 This type is 
also similar to the single layer but it contains a immediate 
drug release layer and other layer will be a controlled 
release along with the adhesive layer. The adhesive layer is 
responsible for the releasing of the drug. This patch also has 
a temporary liner-layer and a permanent backing.
8 
Multi-
layer drug-in-adhesive type transdermal patch has shown in 
figure 3. 
 
 
Figure 3: Multi layer drug in adhesive24 
 
Drug Reservoir-In-Adhesive 
The Reservoir transdermal system design is characterized 
by the inclusion of a liquid compartment containing a drug 
solution or suspension separated from the release liner by a 
semi-permeable membrane and adhesive. The adhesive 
component of the product responsible for skin adhesion can 
either be incorporated as a continuous layer between the 
membrane and the release liner or in a concentric 
configuration around the membrane.
26
 Drug reservoir-in-
adhesive transdermal patch has shown in figure 4. 
 
 
Figure 4: Drug-reservoir-in-adhesive26 
 
Drug Matrix-In-Adhesive 
The Matrix system design is characterized by the inclusion 
of a semisolid matrix containing a drug solution or 
suspension which is in direct contact with the release liner. 
The component responsible for skin adhesion is 
incorporated in an overlay and forms a concentric 
configuration around the semisolid matrix.
24, 27 
Drug-matrix-
in-adhesive type transdermal patch has shown in figure 5. 
 
 
Figure 5: Drug-matrix-in-adhesive26 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1172
Vapour Patch
 
In this type of patch the role of adhesive layer not only 
serves to adhere the various layers together but also serves 
as release vapour. The vapour patches are new to the 
market, commonly used for releasing of essential oils in 
decongestion. Various other types of vapor patches are also 
available in the market which are used to improve the 
quality of sleep and reduces the cigarette smoking 
conditions.
28 
 
Evaluation of tdds 
Physicochemical evaluation 
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 the prepared patch.
8,17 
 
Uniformity of weight 
Weight variation is studied by individually weighing 10 
randomly selected patches and calculating the average 
weight. The individual weight should not deviate 
significantly from the average weight. 
18,28,29 
 
Drug content determination 
An accurately weighed portion of film (about 100 mg) is 
dissolved in 100 ml of suitable solvent in which drug is 
soluble and then the solution is shaken continuously for 24 
h in shaker incubator. Then the whole solution is sonicated. 
After sonication and subsequent filtration, drug in solution 
is estimated spectrophotometrically by appropriate 
dilution.
29,30 
 
Moisture content 
The prepared films are weighed individually andkept in a 
desiccators containing calcium chloride at room 
temperature for 24 h. The films are weighed again after a 
specified interval until they show a constant weight. The 
percent moisture content is calculated using following 
formula.
6,31
 
 
 
 
Uptake Moisture 
Weighed films are kept in a desiccator at room temperature 
for 24 h. These are then taken out and exposed to 84% 
relative humidity using saturated solution of Potassium 
chloride in a desiccator until a constant weight is achieved. 
% moisture uptake is calculated as given below
18, 31 
 
 
Flatness 
 
A transdermal patch should possess a smooth surface and 
should not constrict with time. This can be demonstrated 
with flatness study. For 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. Zero percent 
constriction is equivalent to 100 percent flatness.
28, 32 
 
 
 
L2 = Final length of each strip 
L1 = Initial length of each strip 
 
Folding Endurance 
Evaluation of folding endurance involves determining the 
folding capacity of the films subjected to frequent extreme 
conditions of folding. Folding endurance is determined by 
repeatedly folding the film at the same place until it break. 
The number of times the films could be folded at the same 
place without breaking is folding endurance value
17, 28 
 
Tensile Strength 
To determine tensile strength, polymeric films are 
sandwiched separately by corked linear iron plates. One end 
of the films is kept fixed with the help of an iron screen and 
other end is connected to a freely movable thread over a 
pulley. The weights are added gradually to the pan attached 
with the hanging end of the thread. A pointer on the thread 
is used to measure the elongation of the film. The weight 
just sufficient to break the film is noted. The tensile strength 
can be calculated using the following equation.
8, 18, 28
 
 
 
 
Where, S = tensile stress in 980 dynes/cm2, m = mass in 
grams, g = acceleration due to gravity (980 dynes/cm
2
) 
b = breadth of strip in centimeters, t = thickness of strip in 
centimeters 
 
Water vapor transmission studies (WVT) 
For the determination of WVT, Rao et al., (1997) weighed 
one gram of calcium chloride and placed it in previously 
dried empty vials having equal diameter. The polymer films 
were pasted over the brim with the help of adhesive like 
silicon adhesive grease and the adhesive was allowed to set 
for 5 minutes. Then, the vials were accurately weighed and 
placed in humidity chamber maintained at 68 % RH. The 
vials were again weighed at the end of every 1
st
 day, 2
nd
 
day, 3
rd
 day up to 7 consecutive days and an increase in 
weight was considered as a quantitative measure of 
moisture transmitted through the patch.
33,34
 
 
In other reported method, desiccators were used to place 
vials, in which 200 mL of saturated sodium bromide and 
saturated potassium chloride solution were placed. The 
desiccators were tightly closed and humidity inside the 
desiccator was measured by using hygrometer. The 
weighed vials were then placed in desiccator and procedure 
was repeated. 
 
 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1173
Adhesive studies 
The therapeutic performance of TDDS can be affected by 
the quality of contact between the patch and the skin. The 
adhesion of a TDDS to the skin is obtained by using PSAs, 
which are defined as adhesives capable of bonding to 
surfaces with the application of light pressure. The adhesive 
properties of a TDDS can be characterized by considering 
the following factors: 
� Peel Adhesion properties 
� Tack properties 
� Thumb tack test 
� Rolling ball test 
� Quick stick (Peel tack) test 
� Probe tack test 
� Shear strength properties or creep resistance 
 
Swellability 
The patches of 3.14 cm² was weighed and put in a petridish 
containing 10 ml of double distilled water and were allowed 
to imbibe. Increase in weight of the patch was determined at 
preset time intervals, until a constant weight was observed. 
The degree of swelling (S) was calculated using the formula 
 
 
 
Where S is percent swelling,Wt
 
is the weight of patch at 
time t and W0
 
is the weight of patch at time zero.
33,35
 
 
IN VITRO RELEASE STUDIES 
There are various methods available for determination of 
drug release rate of TDDS. 
� 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 
 
In Vitro Permeation Studies 
Usually permeation studies are performed by placing the 
fabricated transdermal patch with rat skin or synthetic 
membrane in between receptor and donor compartment in a 
vertical diffusion cell such as franz diffusion cell or 
keshary-chien diffusion cell. The transdermal system is 
applied to the hydrophilic side of the membrane and then 
mounted in the diffusion cell with lipophillic side in contact 
with receptor fluid. The receiver compartment is maintained 
at specific temperature (usually 32±5°C for skin) and is 
continuously stirred at a constant rate. Samle analyzed by 
spectrophotometric method.
6, 8,13,17,18,28
 
 
 
 
STRATEGIES TO OVERCOME THE EPIDERMAL BARRIER 
The non-invasive approaches for providing transdermal drug delivery of various therapeutic substances are: 
 
Table 1:Non-invasive approaches. 
Drug and vehicle 
interactions 
Stratum corneum 
modification 
Stratum corneum 
bypassed or removed 
Electrically assisted 
methods 
Vesicles and particles 
1.Selection of correct 
 drug or prodrug 
2.Chemical potential 
 adjustment 
3.Ion pairs and complex 
 coacervates 
4.Eutectic systems 
1.Hydration 
2. Chemical 
 penetration 
 enhancers16 
1.Microneedle array16, 34 
2.Stratum corneum 
ablated 
3.Follicular delivery 16 
 
1.Ultrasound 14, 34 
2. Iontophoresis38 
3.Electroporation14 
4.Magnetophoresis 
5.Pressure wave 
 
1.Liposomes36 
2.Niosomes37 
3.Transfersomes.14,16, 38 
 
 
Marketed Formulation of Transdermal Drug Delivery System 
Table 2: Currently available medications for transdermal delivery 39 
Drug Trade name Manufacturer Indication 
Estradiol Alora TheraTech/Proctol and Gamble Postmenstrual syndrome 
Testosterone 
 
Androderm 
 
TheraTech/GlaxoSmithKline 
 
Hypogonadism (males) 
Clonidine Catapres-TTS Alza/Boehinger Ingelheim Hypertension 
Estradiol Climaderm Ethical Holdings/Wyeth-Ayerest Postmenstrual syndrome 
Estradiol Climara 3M Pharmaceuticals/Berlex Labs Postmenstrual syndrome 
Estradiol/Norethindrone CombiPatch Noven , Inc./Aventis Hormone replacement therapy 
Nitroglycerin Deponit Schwarz-Pharma Angina pectoris 
Fentanyl Duragesic Alza/Janssen Pharmaceutica Moderate/severe pain 
Estradiol Estraderm Alza/Norvatis Postmenstrual syndrome 
Estrogen Fematrix Ethical Holdings/Solvay Healthcare Ltd. Postmenstrual syndrome 
Estradiol FemPatch Parke-Davis Postmenstrual syndrome 
Nicotine Habitraol Novartis Smoking cessation 
Nitroglycerin Minitran 3M Pharmaceuticals Angina pectoris 
Nicotine Nicoderm Alza/GlaxoSmithKline Smoking cessation 
Nicotine Nicotrol Cygnus Inc./McNeil Consumer Products,Ltd. Smoking cessation 
Nitroglycerin Nitrodisc Roberts Pharmaceuticals Angina pectoris 
Nitroglycerin Nitro-dur Key Pharmaceuticals Angina pectoris 
Estrogen/Progesterone Nuvelle TS Ethical Holdings/Schering Hormone replacement therapy 
Nitroglycerin Transderm- Nitro® Alza/Norvatis Angina pectoris 
 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1174
 
 
RECENT WORKES ON TRANSDERMAL DRUG DELIVERY 
 Table 3: Different research works of tdds 
DRUG TYPE OF TRANSDERMAL PATCH METHOD AUTHOR 
Glipizide Matrix transdermal systems Solvent evaporation techniqueSrinivas Mutalik40 
 
 Losartan potassium 
Adhesive transdermal patch Solvent evaporation technique Petkar K.C.,41 
Lercanidipine hydrochloride Matrix type transdermal patches Solvent evaporation technique Mamatha T.,42 
Carvedilol Matrix type transdermal patches Solvent evaporation technique Udhumansha Ubaidulla,43 
Metoprolol succinate Matrix type transdermal patches Solvent casting technique Himansu Bhusan Samal44 
Metformin hydrochloride Matrix type transdermal patches Solvent casting technique Arijit Das45 
Glibenclamide and Atenolol Single-layer patch Solvent Casting technique Posina anitha,46 
Propranolol Adhesive transdermal patch Solvent evaporation technique Alexei L. Iordanskii,47 
Domperidone Matrix type transdermal patches Film casting technique Madishetti S.K.,48 
Dexamethasone Matrix type transdermal patches Solvent evaporation technique Biswajit Mukherjee49 
Amlodipine Adhesive transdermal patch Solvent evaporation technique Yinghua Sun50 
Meloxicam Adhesive transdermal patch Film casting technique Young-Chang Ah51 
Lornoxicam Matrix type transdermal patches Solvent evaporation technique More Mangesh Rajendra52 
Sinomenine Adhesive transdermal patch Salivation method. Yujie Ye53 
Ketoprofen Matrix type transdermal patches Solvent evaporation technique Shashikant D. Barhate54 
Ketorolac 
Tromethamine 
Matrix type transdermal patches Solvent evaporation technique Satyanarayan Pattnaik55 
Atenolol Matrix type transdermal patches Solvent evaporation technique P Eswaramma56 
Celecoxib Matrix type transdermal patches Solvent evaporation technique Gilhotra Ritu Mehra57 
Indomethacin Adhesive transdermal patch Solvent evaporation technique Liang Fang58 
Losartan Potassium Matrix type transdermal patches Solvent evaporation technique Petkar K.C.,59 
 
PATENTS ON TRANSDERMAL DRUG DELIVERY SYSETM 
Table 4: Patents on TDDS and Related research works. 
Patent Number Title Owner Issue Date 
4668232 Transdermal drug patches60 Cordes, et al. 5/26/1987 
4900554 Adhesive device for application to body tissue61 Yanagibashi, et al. 2/13/1990 
4883669 Transdermal absorption dosage unit for estradiol and other estrogenic steroids and 
process for administration62 
Chien, et al. 11/28/1989 
4994267 Transdermal acrylic multipolymer drug delivery system63 Sablotsky 2/19/1991 
5028435 System and method for transdermal drug delivery48 Katz, et al. 7/2/1991 
5120546 Transdermal system64 Hansen, et al. 6/9/1992 
5232702 Silicone pressure sensitive adhesive compositons for transdermal drug delivery 
devices and related medical devices65 
Pfister, et al. 8/3/1993 
5446070 Compositions and methods for topical administration of pharmaceutically active 
agents67 
Mantelle 8/29/1995 
5474783 Solubility parameter based drug delivery system and method for altering drug 
saturation concentration68 
Miranda, et al. 12/12/1995 
5523095 Controlled release matrix system using cellulose acetate/polyvinylpyrrolidone 
blends69 
Wilson, et al. 6/4/1996 
5589498 Transdermal delivery of the active enantiomer of ketorolac70 Mohr, et al. 12/31/1996 
5656286 Solubility parameter based drug delivery system and method for altering drug 
saturation concentration71 
Miranda, et al. 8/12/1997 
5662923 Plaster for the transdermal application of steroid hormones, containing 
dexpanthenol72 
Roreger 9/2/1997 
 
Future Technologies And Approaches 
� Thermal Poration is the formation of aqueous pathways 
across stratum corneum by the application of pulsed 
heat; this approach has been used to deliver 
conventional drugs and to extract intestinal fluid 
glucose from human subjects. 
� Jet injectors are receiving increased attention now 
days, which is opening doors for improved device 
design for controlled, needle free injection of drug 
solutions across the skin and into deeper tissue. 
� Small needle is inserted a few millimeters into skin and 
drug solution is flowed through the needle into the skin 
at controlled rates using a micro‐infusion pump that is 
contained within a large patch affixed to skin, 
morphine has been delivered to humans using this 
approach. 
� During the past decade several theories have been put 
forward in addressing the combinations of chemicals 
and iontophoresis; chemicals and electroporation; 
chemicals and ultrasound; iontophoresis and 
ultrasound; electroporation and iontophoresis; and 
electroporation and ultrasound. 
� TransPharma is focused on products for which our 
technology will provide clear benefits over existing 
therapies. Such benefits could include improving safety 
and compliance through the use of a drug patch or 
enhancing efficacy with the use of sustained release 
patch formulations, among others. 
Research J. Pharm. and Tech. 5(9): September 2012 
 
 1175
� The ViaDerm system may be applied to the delivery of 
local medications for topical applications in the fields 
of dermatology and cosmetics. The ViaDerm system 
may also allowenhanced immunisations, providing a 
nonpainful, safe and effective alternative to current 
intramuscular or subcutaneous vaccination methods. 
� Altea Therapeutics is currently in clinical development 
of a transdermal patch designed to address a major 
unmet need by. 
� Preventing ‘off’ periods and provide an improved 
therapeutic option for managing Parkinson’s disease.
8, 
45, 32.
 
 
Regulatory Strategy For Investigational New Drug 
Application And New Drug Application Submissions 
For Tdds 
� Standard irritation and sensitization studies should be 
performed with the patch itself in animals/ humans. 
� Negotiate the timing and implementation of the 
toxicology requirements. 
� The dermatology division at FDA should review 
dermal aspects of the IND and New drug 
Application(NDA). 
� Primary review should occur at the division that 
handles the indication under study. 
� Dose ranging studies be required in Phase 2.Single 
Phase 3 study could be negotiated.
12,32.
 
 
CONCLUSION: 
Transdermal drug delivery systems have been used as safe 
and effective drug delivery devices. Their potential role in 
controlled release is being globally exploited by the 
scientists with high rate of attainment. If a drug has right 
mix of physical chemistry and pharmacology, transdermal 
delivery is a remarkable effective route of administration. 
Due to large advantages of the TDDS, many new researches 
are going on in the present day to incorporate newer drugs 
via the system. Due to the recent advances in technology 
and the incorporation of the drug to the site of action 
without rupturing the skin membrane transdermal route is 
becoming the most widely accepted route of drug 
administration. This article provides valuable information 
regarding the formulation and evaluation aspects of 
transdermal drug delivery systems as a ready reference for 
the research scientists who are involved in TDDS. The 
foregoing shows that TDDS have great potentials, being 
able to use for both hydrophobic and hydrophilic active 
substance into promising deliverable drugs. To optimize 
this drug delivery system, greater understanding of the 
different mechanisms of biological interactions, and 
polymer are required. TDDS is a realistic practical 
application as the next generation of drug delivery system. 
 
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