Transdermal Drug Delivery Systems (TDDS)

Definition
Transdermal Drug Delivery System (TDDS) are defined as self-contained, discrete dosage forms
which are also known as “patches”, when patches are applied to the intact skin, deliver the drug
through the skin at a controlled rate to the systemic circulation.
In contrast to topical drug delivery, for transdermal drug delivery, the drug migrate through the
skin to the underlying blood supply without buildup in the dermal layers
Introduction
Transdermal drug delivery is the non-invasive delivery of medications from the surface of skin-
the largest and most accessible organ of human body- through its layers, to the circulatory
system. TDDS offers many advantages over conventional injection and oral methods. It reduces
the load that the oral route commonly places on the digestive tract and liver. It enhances patient
compliance and minimizes harmful side effects of a drug caused from temporary overdose.
Another advantage is convenience, especially notable in patches that require only once weekly
application. Such a simple dosing regimen can aid in patient adherence to drug therapy.
Designing and development of transdermal patches can be described as state of the art.
Objective 
The main objective of transdermal drug delivery system is to deliver drugs into systemic
circulation through skin at predetermined rate with minimal inter and intra patient variation.
Development of TDDS 
The development of TDDS is multidisciplinary activity that encompasses fundamental
feasibility. A studies starting from 1) the selection of drug molecule to 2) the demonstration of
sufficient drug flux in an ex vivo and in vivo model followed by 3) fabrication of a drug delivery
system that meets all the stringent needs that are specific to the drug molecule (physicochemical
and stability factors), 4) the patient (comfort and cosmetic appeal), 5) the manufacturer (scale up
and manufacturability) and 6) most important the economy
Transdermal Routes
Skin
The skin is the largest organ of the human body which covers a surface area of approximately 2
Sq. M and receives about one third of the blood circulation through the body. It serves as a
permeability barrier against the transdermal absorption of various chemical and biological
agents. It is one of the most readily available organs of the body with a thickness of few
millimeters (2.97 0.28 mm) which,
- Separates the underlying blood circulation network from the outside environment
- Serves as a barrier against physical, chemical and microbiological attacks.
- Acts as a thermostat in maintaining body temperature.
- Protects against the penetration of UV rays.
- Skin is a major factor in determining the various drug delivery aspects like permeation and
absorption of drug across the dermis.
The Skin Anatomy
The skin is divided histologically into the stratum corneum (the outer layer), the living
epidermis, and the dermis, collectively a laminate of barriers protecting against permeation by
external agents and loss of water from the body. Blood capillaries and nerve fibers rise from the
subcutaneous fat into the dermis and up to the epidermis. Sebaceous glands, sweat glands, and
hair follicles originating in the dermis and subcutaneous layers rise to the skin's surface.

Stratum Corneum
The stratum corneum is the desquamating horny layer, a 10- to 15-mm-thick layer of flat,
partially desiccated, dead epidermal cells. The stratum corneum is composed of approximately
40% protein (mainly keratin) and 40% water, with the balance being lipid, principally as
triglycerides, free fatty acids, cholesterol, and phospholipids.
This horny layer may be modeled as a wall-like structure with protein bricks and lipid mortar. It
consists of horny skin cells (corneocytes) which are connected via desmosomes (protein-rich
appendages of the cell membrane). The corneocytes are embedded in a lipid matrix which plays
a significant role in determining the permeability of substance across the skin. The lipid content
is concentrated in the extracellular phase of the stratum corneum and forms to a large extent the
membrane surrounding the cells. Because a drug’s major route of penetration is through the
intercellular channels, the lipid component is considered an important determinant in the first
step of absorption. On the surface is a thin film of emulsified material composed of a complex
mixture of sebum, sweat, and desquamating epidermal cells.
The stratum corneum, being keratinized tissue, behaves as a semipermeable membrane, and drug
molecules can penetrate by passive diffusion. The rate of drug movement across this skin layer
depends on the drug concentration in the vehicle, its aqueous solubility, and the oil–water
partition coefficient between the stratum corneum and the product's vehicle. Substances with
both aqueous and lipid solubility characteristics are good candidates for diffusion through the
stratum corneum.
Living Epidermis
This is situated beneath the stratum corneum and varies in thickness from 0.06 mm on the
eyelids to 0.8mm on the palms. Going inwards, it consists of various layers as stratum
lucidum, stratum granulosum, stratum spinosum, and the  stratum basale. In the basale layer,
mitosis of the cells constantly renews the epidermis and this proliferation compensates the loss of
dead horny cells from the skin surface. As the cells produced by the basale layer move outward,
they itself alter morphologically and histochemically, undergoing keratinization to form the
outermost layer of stratum corneum.
Dermis
Dermis is the layer of skin just beneath the epidermis which is 3 to 5 mm thick layer and is
composed of a matrix of connective tissues, which contains blood vessels, lymph vessels, and
nerves. The cutaneous blood supply has essential function in regulation of body temperature. It
also provides nutrients and oxygen to the skin, while removing toxins and waste products.
Capillaries reach to within 0.2 mm of skin surface and provide sink conditions for most
molecules penetrating the skin barrier. The blood supply thus keeps the dermal concentration of
permeate very low, and the resulting concentration difference across the epidermis provides the
essential driving force for transdermal permeation. In terms of transdermal drug delivery, this
layer is often viewed as essentially gelled water, and thus provides a minimal barrier to the
delivery of most polar drugs, although the dermal barrier may be significant when delivering
highly lipophilic molecules.
Hypodermis                                              
The hypodermis or subcutaneous fat tissue supports the dermis and epidermis. It serves as a fat
storage area. This layer helps to regulate temperature, provides nutritional support and
mechanical protection. It carries principal blood vessels and nerves to skin and may contain
sensory pressure organs. For transdermal drug delivery, drug has to penetrate through all three
layers and reach in systemic circulation.
Percutaneous Absorption
Before a topically applied drug can act either locally or systemically, it must penetrate
through stratum corneum. Percutaneous absorption is defined as penetration of substances into
various layers of skin and permeation across the skin into systemic circulation. Percutaneous
absorption of drug molecules is of particular importance in transdermal drug delivery system
because the drug has to be absorbed to an adequate extent and rate to achieve and maintain
uniform, systemic, therapeutic levels throughout the duration of use. In general once drug
molecule cross the stratum corneal barrier, passage into deeper dermal layers and systemic
uptake occurs relatively quickly and easily.
Routes of Drug Penetration through skin
In the process of percutaneous permeation, a drug molecule may pass through the epidermis
itself or may get diffuse through shunts, particularly those offered by the relatively widely
distributed hair follicles and eccrine glands. In the initial transient diffusion stage, drug
molecules may penetrate the skin along the hair follicles or sweat ducts and then absorbed
through the follicular epithelium and the sebaceous glands. When a steady state has been
reached the diffusion through the intact  Stratum corneum becomes the primary pathway for
transdermal permeation

Figure: Simplified diagram of skin structure and routes of drug penetration, (a) Macroroutes: (1)
via the sweat ducts; (2) across the continuous stratum corneum; or (3) through the hair follicles
with their associated sebaceous glands, (b) Representation of the stratum corneum membrane,
illustrating two possible microroutes for permeation.
For any molecules applied to the skin, two main routes of skin permeation can be defined:
- Transepidermal route
- Transfollicular route
Transepidermal route
In transepidermal transport, molecules cross the intact horny layer by two potential micro-routes
of entry exist, the transcellular (or intracellular) and the intercellular pathway as shown above.
Both polar and non-polar substances diffuse via transcellular and intercellular routes by different
mechanisms. The polar molecules mainly diffuse through the polar pathway consisting of
“bound water” within the hydrated stratum corneum whereas the non-polar molecules dissolve
and diffuse through the non-aqueous lipid matrix of the stratum corneum. Thus the principal
pathway taken by the drug is decided mainly by the partition coefficient (log K). Hydrophilic
drugs partition preferentially into the intracellular domains, whereas lipophillic permeants
(octanol/water log K > 2) traverse the stratum corneum via the intercellular route. Most
molecules pass the stratum corneum by both routes
Transfollicular route (Shunt pathway)
This route comprises transport via the sweat glands and the hair follicles with their associated
sebaceous glands. Although these routes offer high permeability, they are considered to be of
minor importance because of their relatively small area, approximately 0.1% area of the total
skin. This route seems to be most important for ions and large polar molecules which hardly
permeate through the stratum corneum
Barrier functions of the skin:
The top layer of skin is most important function in maintaining the effectiveness of the barrier.
Here the individual cells overlie each other and are tightly packed, preventing bacteria from
entry and maintaining the water holding properties of the skin. Stratum corneum mainly consists
of the keratinized dead cell and water content is also less as compared to the other skin
components. Lipids are secreted by the cells from the base layer of the skin to the top. These
lipid molecules join up and form a tough connective network, in effect acting as the mortar
between the bricks of a wall.
Basic Principal of Transdermal permeation:
Transdermal transport of drug through the stratum corneum is mainly the molecular passive
diffusion. The physico-chemical and structural properties of the substance determine the capacity
of diffusion and penetration through the membrane: important determinants are solubility and
diffusibility. This passive process of absorption follows Fick's law of diffusion: the velocity of
absorption - flow - is proportional to the difference of concentration of the substance in relation
to that within the barrier. The permeability coefficient relates flow and concentration, resulting
from partition coefficient, diffusion coefficient, and length of diffusion route. Most solute
substances, non-polar or polar, penetrate across intercellular lipid avenues. Skin is the most
intensive and readily accessible organ of the body as only a fraction of millimeter of tissue
separates its surface from the underlying capillary network. The release of a therapeutic agent
from a formulation applied to the skin surface and its transport to the systemic circulation is a
multistep process. The various steps involved in transport of drug from patch to systemic
circulation are as follows:
1. Dissolution of drug within and release from the formulation
2. Diffusion of drug from drug reservoir to the rate controlling membrane
3. Sorption by the stratum corneum and partitioning into the stratum corneum
4. Diffusion through the stratum corneum, principally via a lipidic intercellular pathway
5. Partitioning from the SC into the aqueous viable epidermis, diffusion through the viable
epidermis and into the upper dermis.
6. Uptake of drug by capillary network in the dermal papillary layer and into systemic circulation
7. Effect on the target organ
Properties that influence transdermal drug delivery
Properties that influence transdermal delivery are:
• Release of the medicament from the vehicle
• Penetration through the skin barrier.
• Activation of the pharmacological response.
Advantages of Transdermal Drug Delivery
• Transdermal drug delivery enables the avoidance of gastrointestinal absorption with its
associated pitfalls of enzymatic and pH associated deactivation
• Avoidance of first pass metabolism.
• The lack of peaks in plasma concentration can reduce the risk of side effects, thus drugs that
require relatively consistent plasma levels are very good candidate for transdermal drug delivery.
• As a substitute for oral route.
• The patch also permit constant dosing rather than the peaks and valley in medication level
associated with orally administered medication.
• Rapid notifications of medication in the event of emergency as well as the capacity to terminate
drug effects rapidly via patch removal.
• Avoidance of gastro intestinal incompatibility.
• Convenience especially notable in patches that require only once weekly application, such a
simple dosing regimen can aid in patient adherence to drug therapy.
• Minimizing undesirable side effects.
• Provide utilization of drug with short biological half lives, narrow therapeutic window.
• Avoiding in drug fluctuation drug levels.
• Inter and intra patient variation.
• Termination of therapy is easy at any point of time.
• Provide suitability for self administration.
• They are non invasive, avoiding the inconvenience of parentral therapy.
• The activity of drugs having a short half life is extended through the reservoir of drug in the
therapeutic delivery system and its controlled release.
• It is of great advantages in patients who are nauseated or unconscious.
• Transdermal patches are better way to deliver substances that are broken down by the stomach
acids, not well absorbed from the gut, or extensively degraded by the liver.
• Transdermal patches are cost effective.
Disadvantages of transdermal Drug Delivery
• Transdermal drug delivery system cannot deliver ionic drugs.
• It cannot achieve high drug levels in blood.
• It cannot develop for drugs of large molecular size.
• It cannot deliver drugs in a pulsatile fashion.
• It cannot develop if drug or formulation causes irritation to skin.
• Possibility of local irritation at site of application.
• May cause allergic reaction.
• Sufficient aqueous and lipid solubility, a log P (octanol/ water) between 1 and 3 is required for
permeate to transverse stratum corneum and underlying aqueous layer.
• Only potent drugs are suitable candidates for transdermal patch because of the natural limits of
drug entry imposed by the skin’s impermeability.
• Long time adherence is difficult.
Factors affecting transdermal permeation
Biological factor
Skin conditions
The intact skin itself acts as barrier but many agents like acids, alkali cross the barrier cells and
penetrates through the skin, many solvents open the complex dense structure of horny layer.
Solvents like methanol, chloroform remove lipid fraction, forming artificial shunts through
which drug molecules can pass easily.
Skin age
It is seen that the skin of adults and young ones are more permeable than the older ones but there
is no dramatic difference .Children shows toxic effects because of the greater surface area per
unit body weight, thus potent steroids, boric acid, hexachlorophene have produced severe side
effects.
Blood Supply
Changes in peripheral circulation can affect transdermal absorption.
Regional skin site
Thickness of skin, nature of stratum corneum and density of appendages vary site to site. These
factors affect significantly the drug penetration.
Skin metabolism
Skin metabolizes steroids, hormones, chemical carcinogens and some drugs. So skin metabolism
determines efficacy of drug permeated through the skin.
Species differences
The skin thickness, density of appendages and keratinization of skin vary species to species, so
affects the penetration.
Physicochemical factors
Skin hydration
In contact with water the permeability of skin increases significantly. Hydration is most
important factor increasing the permeation of skin. So use of humectant is done in transdermal
delivery.
Temperature and pH
The permeation of drug increases ten folds with temperature variation. The diffusion coefficient
decreases as temperature falls. 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.
Thus, temperature and pH are important factors affecting drug penetration
Diffusion coefficient
Penetration of drug depends on diffusion coefficient of drug. At a constant temperature the
diffusion coefficient of drug depends on properties of drug, diffusion medium and interaction
between them.
Drug concentration
The flux of drug is proportional to the concentration gradient across the barrier and concentration
gradient will be higher if the concentration of drug will be more across the barrier.
Partition coefficient
The optimal partition coefficient (K) is required for good action. Drugs with high K are not ready
to leave the lipid portion of skin. Also, drugs with low K will not be permeated.
Molecular size and shape
Drug absorption is inversely related to molecular weight, small molecules penetrate faster than
large ones.
Environmental factors
Sunlight
Due to Sunlight the walls of blood vessels become thinner leading to bruising with only minor
trauma in sun-exposed areas. Also pigmentation: The most noticeable sun-induced pigment
change is a freckle.
Cold Season
Often result in itchy, dry skin. Skin responds by increasing oil production to compensate for the
weather’s drying effects. A good moisturizer will help ease symptoms of dry skin. Also, drinking
lots of water can keep your skin hydrated and looking radiant.
Air Pollution    
Dust can clog pores and increase bacteria on the face and surface of skin, both of which lead to
acne or spots. This affects drug delivery through the skin. Invisible chemical pollutants in the air
can interfere with skin’s natural protection system, breaking down the natural skin’s oils that
normally trap moisture in skin and keep it supple.
Effect of Heat on Transdermal patch
Heat induced high absorption of transdermal delivered drugs. Patient should be advised to avoid
exposing the patch application site to external heat source like heated water bags, hot water
bottles. Even high body temperature may also increase the absorption transdermally delivered
drugs. In this case the patch should be removed immediately. Transdermal drug patches are
stored in their original packing and keep in a cool, dry place until they are ready to use.
Formulation of transdermal drug delivery system
Various components of a transdermal drug delivery system are drug reservoir, backing laminate,
rate controlling membrane, adhesive layer and release liner as shown in figure below:
1. Drug Substance
The drug should be chosen with great care for successful development of a transdermal drug
delivery system. The following are some of the desirable properties of a drug for transdermal
delivery.
Physicochemical properties
• The drugs having a molecular weight of less than 1000 Daltons are suitable
• The drug should have some degree of solubility in both oil and water (ideally, greater then
1mg/ml).
• The drug should have melting point less than 200Ċ. Concentration gradient across the
membrane is directly proportional to the log solubility of drug in the lipid phase of membrane,
which in turn is directly proportional to the reciprocal of melting point (in degree absolute of the
drug). In order to obtain the best candidates for TDD, an attempt should be made to keep the
melting point as low as possible.
• A saturated aqueous solution of the drug should have a pH value between 5 and 9. Drugs
highly acidic or alkaline in solution are not suitable for TDD; because they get ionized rapidly at
physiological pH and ionized materials generally penetrate the skin poorly.
• Hydrogen bonding groups should be less than 2.
Biological Properties
• Drug should be very potent; i.e. it should be effective in few mg/day (ideally less than 25mg /
day).
• The drug should have short biological half-life.
• The drug should not be irritant and non-allergic to human skin.
• The drug should be stable when contact with the skin.
• They should not stimulate an immune reaction to the skin.
• Tolerance to the drug must not develop under near zero order release profile of transdermal
delivery.
• Dose is less than 50 mg per day, and ideally less than 10 mg per day.
• The drug should not get irreversibly bound in the subcutaneous tissue.
• The drug should not get extensively metabolized in the skin.
Ideal properties of drug candidate for transdermal drug delivery
Parameter Properties

Dose Less than 20mg/day

Halflife < 10 hrs

Molecular weight <400 Dalton

Melting point <200°C

Partition coefficient 1 to 3

Aqueous Solubility >1mg/Ml

pH of the aqueous saturated solution 5-9

Skin Permeability Coefficient >0.5×10-3cm/h

Skin Reaction Non irritating and non-sensitizing

Oral Bioavailability Low

2. Polymer Matrix / Drug Reservoir
Polymers are the backbone of TDDS. Polymer matrix can be prepared by dispersion of drug in
liquid or solid state synthetic polymer base. Systems for transdermal delivery are fabricated as
multi layered polymeric laminates in which a drug reservoir or a drug polymer matrix is sand
witched between two polymeric layers, an outer impervious backing layer that prevents the loss
of drug through the backing surface and an inner polymeric layer that functions as an adhesive,
or rate controlled membrane.
Ideal Properties of a polymer to be used in transdermal system are:
• Molecular weight, chemical functionality of the polymer should be such that the specific drug
diffuses properly and gets released through it.
• The polymer should be stable.
• The polymer should be nontoxic
• The polymer should be easily manufactured
• The polymer should be inexpensive
• The polymer and its degradation products must be non-toxic.
• Large amounts of the active agent are incorporated into it.
The polymers utilized for TDDS can be classified as:
• Natural Polymers: e.g. cellulose derivatives, zein, gelatin, shellac, waxes, gums, natural rubber
and chitosan etc.
• Synthetic Elastomers: e.g. polybutadiene, hydrin rubber, polyisobutylene, silicon rubber, nitrile,
acrylonitrile, neoprene, butyl rubber etc.
• Synthetic Polymers: e.g. polyvinyl alcohol, polyvinylchloride, polyethylene, polypropylene,
polyacrylate, polyamide, polyurea, polyvinylpyrrolidone, polymethylmethacrylate, etc.
The polymers like cross linked polyethylene glycol, eudragits, ethyl cellulose,
polyvinylpyrrolidone and hydroxypropylmethylcellulose are used as matrix formers for TDDS.
Other polymers like, silicon rubber and polyurethane are used as rate controlling membrane.
3. Penetration Enhancers
These are the chemical compounds that increase permeability of stratum corneum so as to attain
higher therapeutic levels of the drug candidate. Penetration enhancers interact with structural
components of stratum corneum, i.e., proteins or lipids. They alter the protein and lipid
packaging of stratum corneum, thus chemically modifying the barrier functions leading to
increased permeability
Ideal properties of permeation enhancers

• Controlled and reversible enhancing action

• Chemical and physical compatibility with drug and other formulation components

• Should not cause loss of body fluids, electrolytes or other endogenous materials

• Non-toxic, non-allergic, non-irritating

• Pharmacological inertness

• Ability to act specifically for predictable duration

• Odorless, colorless, economical and cosmetically acceptable.

Some commonly used permeation enhancers for TDD are:

• Solvents; Methanol, Ethanol, Dimethyl sulfoxide, Propylene glycol, 2- Pyrrolidone, Isopropyl

myristate.

• Anionic Surfectants; Sodium lauryl sulphate.

• Nonionic surfectants; Sorbiton monolaurate, Pluronic.

• Essential oils; Cardamom oil, Caraway oil, Lemon oil, Menthol, d-Limonene, Linoleic acid.

4. Pressure Sensitive Adhesives

A PSA is a material that helps in maintaining an intimate contact between transdermal system
and the skin surface. It should adhere with not more than applied finger pressure, be aggressively
and permanently tachy, and exert a strong holding force. Additionally, it should be removable
from the smooth surface without leaving a residue. Polyacrylates, polyisobutylene and silicon
based adhesives are widely used in TDDSs. The selection of an adhesive is based on numerous
factors, including the patch design and drug formulation. For matrix systems with a peripheral
adhesive, an incidental contact between the adhesive and the drug and penetration enhancer
should not cause instability of the drug, penetration enhancer or the adhesive. In case of reservoir
systems that include a face adhesive, the diffusing drug must not affect the adhesive. In case of
drug-in-adhesive matrix systems, the selection will be based on the rate at which the drug and the
penetration enhancer will diffuse through the adhesive. Ideally, PSA should be physico-
chemically and biologically compatible and should not alter drug release.
5. Backing Laminate
While designing a backing layer, the consideration of chemical resistance of the material is most
important. Excipient compatibility should also be considered because the prolonged contact
between the backing layer and the excipients may cause the additives to leach out of the backing
layer or may lead to diffusion of excipients, drug or penetration enhancer through the layer. The
most comfortable backing will be the one that exhibits lowest modulus or high flexibility, good
oxygen transmission and a high moisture vapor transmission rate. Examples of some backing
materials are vinyl, polyethylene and polyester films.
6. Release Liner
During storage the patch is covered by a protective liner that is removed and discharged
immediately before the application of the patch to skin. It is therefore regarded as a part of the
primary packaging material rather than a part of dosage form for delivering the drug. 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. Typically, release liner 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
up of silicon or Teflon. Other materials used for TDDS release liner include polyester foil and
metallized laminates.
7. Other Excipients
Various solvents such as chloroform, methanol, acetone, isopropanol, and dichloromethane are
used to prepare drug reservoir. In addition, plasticizers such as dibutylpthalate, propylene glycol
are added to provide plasticity to the transdermal patch.
Major Transdermal Drug Delivery Systems

1. Drug in Adhesive System

Single layer drug in adhesive:

The adhesive layer of this system contains the drug. In this type of patch the adhesive layer not
only serves to adhere the entire the various layers together, along with system to the skin, but is
also responsible for releasing of the drug. The rate of release of drug from this type of system is
dependent on the diffusion across the skin. The adhesive layer is surrounded by a temporary
linear and a backing layer.
Multi layer drug in adhesive

The multi-layer drug in adhesive patch is similar to the single-layer system in that both adhesive
layers are also responsible for the releasing of the drug

One of the layer is for immediate release of the drug and other layer is for control release of drug
from the reservoir. The multi-layer patch also has a temporary liner layer and a permanent
backing.
2. Reservoir System
Unlike the single layer and multilayer drug in adhesive systems the reservoir transdermal system
has a separate drug layer. The Reservoir system 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. This patch is also backed by the backing layer. In this type
of system the rate of release is zero order.
3. Drug Matrix in Adhesive System
The Matrix system design has a drug layer of a semisolid matrix containing a drug solution or
suspension. 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
adhesive layer in this patch surrounds the drug layer partially overlying it. These type of patches
are also known as monolithic device.
Desirable Features of TDDS

• Composition relatively invariant in use.

• System size reasonable.

• Defined site for application.

• Application technique highly reproducible.

• Delivery is zero order.

• Delivery is efficient.

Evaluation

The transdermal patches can be characterized in terms of following parameters:

Thickness

The thickness of transdermal film is determined by travelling microscope, dial gauge, screw
gauge or micrometer at different points of the film.

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.

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.

Content uniformity test

10 patches are selected and content is determined for individual patches. If 9 out of 10 patches
have content between 85% to 115% of the specified value and one has content not less than 75%
to125% of the specified  value, then transdermal patches pass the test of content uniformity. But
if  3 patches have content in the range of 75% to 125%, then additional 20 patches are tested for
drug content. If these 20 patches have range from 85% to 115%, then the transdermal patches
pass the test. 

Moisture content

The prepared films are weighed individually and kept 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.

% Moisture content = Initial weight – Final weight X 100

Moisture Uptake

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.      

% moisture uptake = Final weight – Initial weight X 100

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.

% constriction = I1 – I2 X 100 Where I2 = Final length of each strip and

I1 = 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.

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.

Tack properties

It is the ability of the polymer to adhere to substrate with little contact pressure. Tack is
dependent on molecular weight and composition of polymer as well as on the use of tackifying
resins in polymer.

Thumb tack test

The force required to remove thumb from adhesive is a measure of tack.

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.