NAGPUR COLLEGE OF PHARMACY

TRANSDERMAL DRUG DELIVERY SYSTEM

Skin Patches

PRESENTED BY

SIDDHI SHRIGIRIWAR
Nagpur, Maharashtra, India
Email- sshrigiriwar9@gmail.com
 TRANSDERMAL DRUG DELIVERY SYSTEM

CONTENTS

Backing
INTRODUCTION
Drug
PATCHES
APPROACH Membrane
PERMEATION THROUGH SKIN
BASIC COMPONENTS Adhesive
FORMULATION
Linear
EVALUATION
ADVANTAGES
Medicated Transdermal Patch
DISADVANTAGES
 TRANSDERMAL DRUG DELIVERY SYSTEM

INTRODUCTION
➢ Transdermal Drug Delivery System (TDDS) uses self-contained patches to give drugs
topically.
➢ Skin application allows for regulated drug delivery into the bloodstream over time, improving
therapeutic efficacy and minimizing unwanted effects.
➢ A transdermal or skin patch is a medicated adhesive patch put to the skin to deliver a
particular amount of medicine into the bloodstream.
➢ TDDS keeps drug concentrations within the therapeutic window over extended periods,
preventing levels from falling below the minimum or exceeding the maximum effective
concentration.
• Improvepatient compliance
Characteristics • Enhance therapeutic efficiency
• Exhibit skinpenetration
PATCHES

Medicated adhesive patch non-toxic and non-carcinogenic

P exhibit good mechanical strength

Applied on the skin to transfer a particular dose to the R
systemic circulation O
P
do not encounter drug leakage
E
R
T
Maintains drug concentration can incorporate various drugs
I
E
S
The effective concentration
{Avoid overdosing}
APPROACH

TRANSDERMAL DRUG DELIVERY SYSTEM

Membrane Permeation Controlled System

Adhesive Dispersion Type System

Preparation of matrix solution
Coating of matrix layer
Making multilayer laminates
Separate unit
Packaging

Matrix Diffusion Controlled System

Micro-sealed Dissolution System or Encapsulation

CLASSIFICATION

TDDS

Rate-programmed system Physical stimuli

{Transdermal patches} {Activated system}

Drug in reservoir
{Membrane type} Structure-based system
{ecgc microneedles}
Drug in matrix
{{Monolithic type} Velocity-based system
{ecgc get propulsion}
Drug in adhesive
{Matrix}
Electrically-based system
{ecgc iontophoresis
Drug in micro-reservoir Sonophoresis}
{reservoir in the adhesive matrix}
 TRANSDERMAL DRUG DELIVERY SYSTEM

Backing Backing
Drug
Adhesive Drug Membrane
Liner Adhesive
Liner
Drug in matrix
CLASSIFICATION Drug in reservoir
{Monolithic type}
{Membrane type}
TDDS
Backing

Drug + Adhesive Backing

Membrane

Liner Drug + Adhesive

Liner
Drug in micro-reservoir
Drug in adhesive
{reservoir in the adhesive
{Matrix}
matrix}
 TRANSDERMAL DRUG DELIVERY SYSTEM

➢ The TDDS targets systemic medicine levels through topical

application on healthy skin. The human skin's structural
and biochemical properties affect its barrier function and PERMEATION THROUGH SKIN
medication absorption rate.
➢ Access into the body through the skin should be
considered when developing TDDS.

➢ The skin is divided into two layers: the epidermis and the
dermis, sometimes known as the corium. Epidermis
➢ Hair shafts and gland ducts can penetrate these layers.
Skin is the largest organ in the human body, covering Dermis
around 2m2 in an average adult. The skin consists of
three layers: Subcutaneous
➢ the fatty subcutaneous layer (hypodermis), tissue
➢ connective tissue dermis,
➢ and stratified avascular cellular epidermis.
 TRANSDERMAL DRUG DELIVERY SYSTEM

➢ Skin receives around one-third of all blood that circulates throughout the body. The
epidermis, which is 150 m thick, is made up of active basal cells. The outermost layer of the
skin undergoes differentiation, resulting in migration.
➢ Cells move from the basal layer to the skin's surface. The epidermis relies on the transfer of
nutrients and waste products across the dermal-epidermal junction to maintain its strength
as it lacks blood vessels. The epidermis is made up of five layers:
➢ stratum germinate vum (base layer),
➢ stratum spinosum (spinous layer),
➢ stratum granulosum (granular layer),
➢ stratum lucidium, and
➢ stratum corneum (SC),
➢ arranged from inside to outside. The epidermis without the SC layer is referred to as the
viable epidermis because the SC cells have died. The SC layer is the rate-limiting barrier in
transdermal.
 TRANSDERMAL DRUG DELIVERY SYSTEM

FACTORS AFFECTING PERMEATION

Physicochemical properties of penetrant
• Partition Coefficient

• pH condition

Physicochemical properties of delivery system

Factors • Affinity
{TDDS} • Composition of drug delivery

Physiological and pathological skin condition

• Skin age

• Lipid film

• Skin hydration and temprature

• Pathological Injury to Skin

 TRANSDERMAL DRUG DELIVERY SYSTEM

BASIC COMPONENTS

Polymer matrix/drug reservoir,

Membrane,
Drug,
Permeation enhancers,
Pressure-Sensitive Adhesives (PSA),
Backing laminates,
Release liner, and
Other excipients.
TRANSDERMAL DRUG DELIVERY SYSTEM

Backing
Patch
Drug

Membrane

Adhesive

Linear
Drug delivery to systemic circulation
 TRANSDERMAL DRUG DELIVERY SYSTEM

Polymer Matrix and Drug Reservoir

➢ Polymers are the backbone of TDDS, controlling medication release from the device. A
polymer matrix can be created by scattering drugs in a liquid or solid form.
➢ A synthetic polymer basis. In TDDS, use biocompatible and chemically compatible
polymers with the drug and other system components (e.g., penetration enhancers and
PSAs). When selecting a polymer for TDDS, consider the following criteria:
➢ The polymer's molecular weight, glass transition temperature, and chemical properties
should facilitate drug diffusion and release.
➢ The polymer should be stable, non-reactive with the medicine, easy to make into the
required product, and affordable.
➢ The polymer and its degradation products should be non-toxic.
➢ aggressive toward the host.
➢ Incorporating substantial amounts of active chemicals should not negatively impact the
polymer's mechanical properties.
 TRANSDERMAL DRUG DELIVERY SYSTEM

Examples of some regularly used polymers for TDDS include:

1) Natural polymers include cellulose derivatives, zein, gelatin, shellac, waxes, proteins, gums,
natural rubber, and starch.
2) Synthetic elastomers include polybutadiene, silicone rubber, nitrile, acrylonitrile, butyl rubber,
styrene-butadiene rubber, and neoprene.
3) Synthetic polymers include polyvinyl alcohol, polyvinyl chloride, polyethylene, polypropylene,
polyacrylate, polyamide, polyurea, polyvinyl pyrrolidone, polymethyl methacrylate, and epoxy.

Membrane

A membrane is either sealed to the backing to create a patch enclosing the drug-containing matrix
or employed as a single layer in the patch creation.
The membrane's diffusion qualities affect the delivery of drugs and excipients to the skin. Rate-
controlling membranes include ethylene vinyl acetate, silicone rubber, and polyurethane, among
others are the examples.
 TRANSDERMAL DRUG DELIVERY SYSTEM

Drug

A TDDS formulation requires careful selection of the medicament to be integrated.

The drug parameters necessary for an ideal drug candidate for TDDS are classified into:

1) Physical-chemical properties: This includes:

➢ The drug's molecular weight should be less than 1000 Daltons.
➢ The medication should have an affinity for both lipophilic and hydrophilic phases.
➢ Extreme partitioning characteristics do not promote effective medication delivery.
➢ The medication should have a low melting point.
➢ To prevent skin injury, use solutions with a pH range of 4.2–5.6. However, certain
medications undergo transdermal absorption at pH values where the drug's unionized form
is prominent.
 TRANSDERMAL DRUG DELIVERY SYSTEM

2) Biological Properties:
The medicine should be powerful, requiring a daily dose of a few milligrams.
The drug's half-life should be short.
The medicine should not irritate or cause allergies.
Drugs that break down in the GI tract or are inactivated by hepatic first-pass metabolism can
be incorporated into TDDS.
Examples include Nicardipine hydrochloride, Captopril, Atenolol, Metoprolol tartrate,
Clonidine, Propranolol hydrochloride, Carvedilol, Verapamil hydrochloride, and Nitrendipine.

Permeation Enhancers

Permeation enhancers, also known as sorption promoters or accelerants, can improve TDDS
levels. These drugs improve the permeability of the SC.
layer to achieve greater therapeutic amounts of the medication. Permeation enhancers interact
with structural components of the SC layer, altering barrier functions and increasing
permeability.
 TRANSDERMAL DRUG DELIVERY SYSTEM

An optimal penetration enhancer should possess the following characteristics:

➢ It must be pharmacologically inactive, affordable, and cosmetically acceptable.
➢ It should be non-toxic, irritant-free, and hypoallergenic.
➢ It should have reversible effects on the stratum corneum's barrier properties.
➢ It needs to be chemically and physically compatible with the TDDS.
➢ It should be easily integrated into the TDDS.
The approaches are as follows:
Chemical enhancers: Chemicals known as accelerators, absorption promoters, or penetration
enhancers are used to increase drug penetration when applied topically. Chemical enhancers
function in the following ways:
Co-solvents improve medication thermodynamic action.
They improve the drug's partition coefficient, allowing for easier release from the vehicle to the
skin.
They prepare the SC layer to promote drug diffusion.
They increase penetration and create a drug reservoir in the SC layer. Examples- DMSO, Oleic
acid, methanol, EDTA, methanol, propylene glycol, lauric aid, azone.
 TRANSDERMAL DRUG DELIVERY SYSTEM

Pressure-Sensitive Adhesives (PSAs)

PSAs are materials that adhere to a substrate (skin in TDDS) with the application of light force and
leave behind no residue on removal. These materials form interatomic and intermolecular
attractive forces at the interface, only when they are in intimate contact. This degree of contact can
be obtained if the material is sensitive to pressure, i.e., it deforms under slight pressure. Adhesion
involves a liquid-like flow, thus the adhesives make the skin surface wet on the application of
pressure; while the adhesive sets in that state on the removal of pressure. Pressure-sensitive
adhesives (PSAs). Examples- are acrylic acid, hydrocarbon resin, silicone-based PSAs.
PSAs stick to a substrate (skin in TDDS) with light force, leaving no residue upon removal. These
materials form.
At the interface, attractive forces between atoms and molecules only exist when they are nearby.
The material can achieve this level of touch if it is pressure-sensitive and deforms under light
pressure. Adhesives create a liquid-like flow that wets the skin surface when pressure is applied
and then sets when pressure is released.
 TRANSDERMAL DRUG DELIVERY SYSTEM
Backing Laminates

Backings provide TDDS a distinct appearance, flexibility, and occlusion. Therefore, the material's
chemical resistance should be important.
Considered when creating a backing layer. Excipient compatibility is important because
prolonged interaction between the backing layer and excipients might cause excipients to be
leached or drugs to diffuse through the layer. The ideal backing has low modulus or high
flexibility, excellent oxygen transfer, and a high moisture vapor transmission rate. Backing
materials include vinyl, polyethylene, polyester, aluminum, and polyolef films.

Release Liner

During storage, the transdermal patch is wrapped with a protective liner. The liner is removed
and discarded before the patch is applied to the skin. The
The liner should be chemically inert as it is in close contact with the transdermal patch. A release
liner consists of either a non-occlusive base layer (e.g., paper fabric) or an occlusive base layer
(e.g., polyethylene, polyvinyl chloride) with a silicon or Teflon coating. TDDS-release liners can be
made of polyester foil or metalized laminates.
 TRANSDERMAL DRUG DELIVERY SYSTEM

FORMULATION
 TRANSDERMAL DRUG DELIVERY SYSTEM

EVALUATION
➢ Interaction Studies: Excipients are a key component of most pharmacological dosage
formulations. The stability of a formulation depends on drug-excipient compatibility. Only the
medicine can develop a steady product.
➢ To ensure the drug's bioavailability and stability, it's important to discover any potential
physical or chemical interactions with its excipients. When using new excipients that have
not previously been utilized in formulations with the active component, compatibility tests
are crucial for formulation development. Thermal analysis, FTIR, UV spectroscopy, and
chromatography are used to conduct interaction studies by comparing physicochemical
properties such as assays, melting endotherms, distinctive wave numbers, and absorption
maxima.

➢ Patch Thickness: Drug-loaded patches are measured at various spots using a digital
micrometer. The average thickness and standard deviation are calculated to assure accuracy.
➢ The thickness of the prepared patch is within the standard range.
 TRANSDERMAL DRUG DELIVERY SYSTEM

➢ Weight Uniformity: Before testing, the patches are dried at 60°C for 4 hours. A digital balance
is used to weigh a particular area of a patch cut from various elements. Individual weights are
used to generate averages and standard deviations.

➢ Drug Content: The drug is dissolved in a specific area of the prepared patch using an
appropriate solvent in a certain volume. The solution is filtered through a media, and the drug
content is measured using UV.

➢ Peel Adhesion Test: Spectroscopy or HPLC techniques. The values are the average of three
distinct samples. The peel adhesion test measures the force required to remove an adhesive
coating from a test substrate. Peel adhesion qualities are determined by the adhesive
polymer's molecular weight, as well as the additives used. This test involves applying a single
tape to either a stainless steel plate or a suitable backing membrane. The tape is pulled from
the substrate at a 180-degree angle, and the force required for removal, has greater strength.
 TRANSDERMAL DRUG DELIVERY SYSTEM

➢ In vitro Drug Release Studies: USP apparatus V (paddle over disc) is used for determining drug
release from the prepared patches. Dry films of known thickness are cut in a definite shape,
weighed, and fixed over a glass plate with an adhesive. The glass plate is placed in 500ml of
dissolution medium or phosphate buffer (pH 7.4) and the apparatus is equilibrated to 32±0.5
C. The paddle is set at a distance of 2.5cm from the glass plate and operated at a speed of 50
rpm. Samples of 5ml aliquots are withdrawn at appropriate time intervals for up to 24 hours
and analyzed by UV spectroscopy or HPLC technique. This experiment is performed in
triplicate to calculate the mean value. In vitro drug release studies use USP equipment V
(paddle over disc) to determine drug release from prepared patches. Dry films of a specific
thickness are cut, weighed, and placed on a glass plate.
➢ Use an adhesive. The glass plate is inserted in 500ml of dissolving medium or phosphate
buffer (pH 7.4) and the apparatus is equilibrated to 32±0.5°C.
➢ The paddle is placed at 2.5cm from the glass plate and rotates at 50 rpm. Samples of 5ml are
taken at regular intervals for up to 24 hours and analyzed using UV spectroscopy or HPLC
techniques. The mean value is calculated by repeating the experiment three times.
 TRANSDERMAL DRUG DELIVERY SYSTEM

➢ In vitro Skin Permeation Studies: Diffusion cells are used for this test. Male Wistar rats
(weighing 200-250gm) are selected and belly hair is removed with an electric clipper.
➢ To apply the diffusion, wipe the skin well with distilled water, equilibrate it for an hour in
dissolving medium or phosphate buffer (pH 7.4), and then place it on a magnetic stirrer with a
small magnetic needle for even distribution.
➢ A thermostatically controlled heater regulates the cell temperature to 32±0.5°C. The isolated
rat skin is inserted between the diffusion cell compartments, with the epidermis pointing
upward into the donor compartment.nAt regular intervals, a specific amount of sample is
taken from the receptor compartment and replaced with the new medium. Samples pass
through the filtering media, and
➢ UV spectroscopy or HPLC was used to analyze the samples. The slope of the curve between the
steady state values of drug permeation (mg/cm2) and time (hours) can be used to measure
flux. Permeability coefficients can be calculated by dividing the flux by the initial drug load
(mg/cm2).
TRANSDERMAL DRUG DELIVERY SYSTEM

Backing
Patch
Drug

Membrane

Adhesive

Linear
Drug delivery to systemic circulation
ADVANTAGES
DISADVANTAGES
THANK YOU
-SIDDHI SHRIGIRIWAR