Transdermal Drug Delivery

SystemPresented by –Natraj S. Adhikari

M.pharm. (Pharmaceutics)

Enrolment no.- A10647013016

Amity institute of Pharmacy

Contents

Introduction

Advantages

Disadvantages

The skin

Routes of penetration

Types of patches

Evolution

In-vitro skin penetration study

Popular uses

References

Introduction

Transdermal drug delivery system is defined as self contained, discrete dosage form, which

when applied to the intact skin deliver the drug through skin at control rate to the systemic

circulation[1].

Skin is used for the delivery of drug because skin has large surface area, there is systemic

access through underlying circulatory and lymphatic networks and it is the non invasive

nature of drug delivery.

Advantages

They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH,

enzymatic activity, and drug interactions with food, drink, and other orally administered drugs.

They can substitute for oral administration of medication when this route is unsuitable, as with

vomiting and diarrhoea

They avoid the first-pass metabolism.

They are non invasive, avoiding the inconvenience of Parenteral therapy

They provide extended therapy with a single application, improving compliance over other

dosage forms requiring more frequent dose administration

Drug therapy may be terminated rapidly by removal of its application from the surface of the

skin

They are easily and rapidly identified in emergencies (for example, unresponsive,

unconscious, or comatose patient) because of their physical presence, features, and identifying

markings.

Disadvantages

Only relatively potent drugs are suitable candidates for transdermal delivery because of the

natural limits of drug entry imposed by the skin’s impermeability

Some patients develop contact dermatitis at the site of application from one or more of the

system components, necessitating discontinuation

The delivery system cannot be used for drugs requiring high blood levels.

The use of transdermal delivery may be uneconomical

This route is limited when the drug is extensively metabolized in the skin and when molecular

size is great enough to prevent the molecules from diffusing through the skin

For a drug,which doesn’t possess a favourable o/w partition coefficient this route cannot be

used[2].

Transdermal drug permeation

In order to design successful transdermal drug delivery system it is important to understand the anatomy and

physiology of skin[3]

figure no.-1

Drug penetration pathways

Figure no.-2

Main component of transdermal patches

Polymers –

These polymers control the release of the drug from the drug reservoir. ·

Natural polymers - Shellac, gelatin, waxes, gums, starch etc

Synthetic polymers- Polyvinyl alcohol, polyethylene, poly- amide, polypropylene, polyurea,

polymethyl- methacrylate etc.

Permeation enhancers –

Substances which temporarily diminish the impermeability of the skin are known as accelerants or

sorption promoters or penetration enhancers These include water, pyrrolidones, fatty acids and

alcohols, azone and its derivatives, alcohols and glycols, essential oils, terpenes and derivatives,

sulfoxides like dimethylsulfoximide (DMSO) and their derivatives, urea and surfactants

Main component of transdermal patches

Adhesives –

It serves to adhere the patch to the skin for systemic delivery of drug. The adhesive must

possess sufficient adhesion property so that the TDDS should remain in place for a long time.

Commonly used adhesives are silicone adhesives, polyisobutylenes adhesives and poly acrylate

based adhesives

Backing layer –

It protects the patch from the outer environment. The backing layer should be impermeable to

drug and penetration enhancers. It does a function of holding the entire system

Types of Transdermal Patches

1. Single-layer Drug-in-Adhesive

2. Multi-layer Drug-in-Adhesive

3. Reservoir type

4. Matrix type

1. Single-layer Drug-in-Adhesive

The adhesive layer of this system also contains the drug. In this type of patch the adhesivelayer not only serves to adhere the various layers together, along with the entire system to theskin, but is also responsible for the releasing of the drug. The adhesive layer is surrounded by atemporary liner and a backing.

figure no.-3

2. 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. The multi-

layer system is different however that it adds another layer of drug-in-adhesive,

usually separated by a membrane (but not in all cases). This patch also has a

temporary liner-layer and a permanent backing.

Figure no.-4

3- Reservoir type

Unlike the Single-layer and Multi-layer Drug-in adhesive systems the reservoir

transdermal system has a separate drug layer. The drug layer is a liquid

compartment containing a drug solution or suspension separated by the adhesive

layer. This patch is also backed by the backing layer. In this type of system the

rate of release is zero order.

Figure no.-5

4-Matrix type

The Matrix system has a drug layer of a semisolid matrix containing

a drug solution or suspension. The adhesive layer in this patch

surrounds the drug layer partially overlaying it.

Figure no.-6

Evaluation

Thickness of patch

The thickness of transdermal film is determined by traveling microscope, dial gauge, screw gauge

or micrometer at different points of the film.

Drug content

An accurately weighed portion of film (about 100mg) 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

by appropriate dilution is estimated spectrophotometrically.

Folding endurance

A strip of specific area was cut evenly and repeatedly folded at the same place till it broke. The

number of times the film could be folded at the same place without breaking gave the value of the

folding endurance

Percentage Moisture content

The prepared films are weighed individually and kept in a desiccators containing calcium chloride at

room temperature for 24h. The films are weighed again after a specified interval until the show a

constant weight. The percent moisture content is calculated as the difference between final and

initial weight with respect to final weight

Percentage Elongation break test

The percentage elongation break was determined by noting the length just before the break point,

the percentage elongation can be determined from the below mentioned formula:

Where, L1is the final length of each strip and L2 is the initial length of each strip

Weight uniformity

The prepared patches were dried at 60°c for 4hrs before testing. A specified area of patch was

cut in different parts of the patch and weigh in digital balance. The average

weight and standard deviation values are to be calculated from the individual weight.

Thumb tack test:

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

Rolling ball test:

This test involves measurement of the distance that stainless steel ball travels along an upward

facing adhesive. The less tacky the adhesive, the further the ball will travel.

In vitro permeation studies:

The in vitro diffusion study was carried out with the abdominal rate skin using Franz diffusion

cell. The cylinder consists of two chambers, the donor and the receptor compartment. The donor

compartment was open at the top and was exposed to atmosphere. The temperature was

maintained at 37 ± 0.5o C and receptor compartment was provided with sampling port. The

diffusion medium used was phosphate buffer (pH 7.4). The diffusion studies were done to get an

idea of permeation of drug through barrier from the transdermal system. In vitro studies are also

done for TDDS development.

Figure no.- 6

In-vivo evaluation

Skin irritation study

Skin irritation and sensitization testing can be performed on healthy

rabbits (average weight 1.2 to 1.5 kg). The dorsal surface (50 cm2) of

the rabbit is to be cleaned and the hair removed from the clean dorsal

surface by shaving and the surface cleaned by using rectified spirit

with the representative formulations applied over the skin. The patch is

to be removed after 24 h and the skin observed and classified into 5

grades on the basis of the severity of skin injury (

Novel advanced technologies

Physical approach Chemical approach Biological

approach

Recent approach

Stripping of stratum

corneum

Delipidization of

stratum corneum

Synthesis of

lipophilic analogs

Use of skin

metabolism

inhibitors

Vesicular approaches

Electroporation Synthesis of

lipophilic analog

Synthesis of

bio-convertible

prodrugs

Microfabricated

microneedles and

micro chips

Thermal energy Sorption promoters

Iontophoresis

[4]

Popular uses

The first commercially available vapour patch of nicotinewas introduced in

America in 1923 to reduce smoking.

Two opioid medications used to provide round-the-clock relief for severe pain are

often prescribed in patch form: Fentanyl(marketed as Duragesic) and

Buprenorphine (marketed as BuTrans).

Estrogen patches are sometimes prescribed to treat menopausal symptoms as well

as post-menopausal osteoporosis.

The anti-hypertensive drug Clonidine is available in transdermal patch form under

the brand name Catapres-TTS[4].

Reference

1. Gaikwad, A. K. (2013). Transdermal drug delivery system: Formulation.Comprehensive Journal of Pharmaceutical Sciences, 1-10.

2. Patel, H.(2012). Transdermal drug delivery system as prominent dosage formsfor the highly lipophilic drugs. International journal of pharmaceutical researchand bio-science, 1(3), 42-65.

3. Pandey, S(2013). An Overview on Transdermal Drug Delivery System.International journal of pharmaceutical and chemical sciences, 1171-1180.

4. Dhote V., P. B. (2011). Iontophoresis: A Potential Emergence of a TransdermalDrug Delivery System. scientia pharmaceutica, 1-28.

5. Kumar SR, Jain A, Nayak S. Development and Evaluation of Transdermalpatches of Colchicine. Der Pharmacia Lettre. 2012, 4 (1):330-343.

6. Vyas SP, Khar RK. Controlled Drug Delivery: Concepts and Advances, firstedition, Vallabh Prakashan, 2002; 411- 447