Information about Transdermal drug delivery system and some important transdermal patches that are available in the market and their uses.

1. PRESENTATION ON TRANSDERMAL DRUG
DELIVERY SYSTEMS
BY
VASANTHI. JONNALAGADDA

2. CONTENTS :
1.Introduction
2.Applications
3.Advantages
4.Disadvantages
5.Structure of Skin
6.Basic components of TDDS
7.Types of TDDS
8.Evaluation

3. INTRODUCTION :
TDDS are defined as self contained , self discrete dosage
forms which when applied to the intact skin deliver the drug at a
controlled rate to the systemic circulation.
A simple patch that you stick onto your skin like an adhesive
bandage, which utilise passive diffusion of drug across skin as the
delivery mechanism.

4. Applications:
• Scopolamine patches are commonly used for treatment of motion
sickness.
• Nicotine patches are the most commonly used
transdermal patches used for cessation of smoking.
• Nitroglycerine patches are sometimes used for the treatment of angina
pectoris
• Rotigotine patches are prescribed for parkinson's disease.
• Estrogen patches are used in certain patients for the treatment of post-
menopausal osteoporosis as well as menopausal symptoms.
• Fentanyl patches are used for the treatment of moderate to
severe pain related to osteo and rheumatoid arthritis.
• Testosterone patches are prescribed for hypogonadism in males.
• Clonidine, an antihypertensive drug, is also available as transdermal

5. • 1% diclofenac transdermal patches are used for local treatment of ankle
sprain and pain in epicondylitis.
• Lidocaine patches are sometimes prescribed for the symptomatic relief
of neuropathic pain associated with post-herpetic neuralgia.
• Estradiol patches are used for HRT.

6. ADVANTAGES:
TDDS offers many advantages over conventional dosage forms ;
o They are associated with low risk to digestive tract or liver.
o They enhance patient compliance due to their non-invasiveness.
o They reduce the harmful side effects of drugs caused due to
temporary overdose
o Self administration is easy.
o They prolong the steady release of drug molecules
thereby preventing the need for frequent dosing.
o Prevent First pass metabolism, GI irritation, low absorption which are
mainly seen in oral dosage forms.

7. DISADVANTAGES:
 Toxicity may occur due to dose dumping.
 Expensive.
 Development of tolerance is very rapid.
 Increased stability problems.
 Skin irritation or contact dermatitis are common.
 The barrier functions of skin vary from person to person with age, and
even from site to site in the same person.

8. STRUCTURE OF THE SKIN :
Anatomically there are many histological layers but they are
divided into three layers:-
1. Epidermis
2. Dermis
3. Subcutaneous layer

9. EPIDERMIS :
 Epidermis have following layers stratum corneum and stratum
germinativum.
 The stratum corneum forms the outermost layer of epidermis and
consists of many layers of compacted, flattened, dehydrated,
keratinized cells in the stratified layer.
 Water content of stratum corneum is around 10% to maintain
flexibility and softness.
 The stratum corneum is responsible for the barrier function of the
skin and behaves as a primary barrier to the percutaneous
absorption.
 It is made up of three layers in thicker parts stratum granulosum,
stratum lucidum, stratum spinosum.

10. DERMIS :
o Dermis is called TRUE SKIN.
o The dermis is made up of regular network of robust collagen of fairly
uniform thickness with regularly placed cross striations.
o The network or the cell gel structure is responsible for the elastic
properties of skin.
o Below the dermis there is a fat containing subcutaneous tissue.
o Upper portion of the dermis is formed into ridges containing
lymphatics and nerve endings.
Structurally dermis has two layers
a. Upper papillary layer
b. Lower reticular layer

11. Subcutaneous:
 This is a sheet of fat containing areolar tissue known as
superficial fascia, attaching the dermis to the underlying
structures.
 It is not a part of the skin it insulates the body from heat
and cold it protects the organs from injury as a shock
absorber.

12. PERMEATION THROUGH SKIN:
The permeation through the skin occurs by the following
routes-
 Transepidermal absorption
 Transfollicular (shunt pathway absorption)
 Clearence by local circulation

13. Pathways of permeation through skin

14. TRANSEPIDERMAL ABSORPTION :
• Stratum corneum is the main resistance for absorption through
this route. So it is called rate limiting membrane.
• Permeation involves partitioning of the drug into stratum
corneum.
• Permeation through the skin depends upon the o/w
distribution tendencies of the drug.
• Lipophilic drug concentrate in and diffuse with relative ease.
• Diffusion of drug from TDDS to stratum corneum, sorption
through stratum corneum and penetration through viable
epidermis then uptake of drug by capillary network
• Finally effect on target organ.

15. TRANSFOLLICULAR ABSORPTION:
• The skin appendages (sebaceous and eccrine sweat
glands) are considered as shunts for bypassing the stratum
corneum.
• Follicular route is important for permeation because the
opening of the follicular pore is relatively large and
sebum aids in diffusion of the penetrant.
• Partitioning into the sebum followed by the diffusion to the
depths of the epidermis is the mechanism.

16. CLEARENCE BY LOCAL CIRCULATION :
 The earliest point of entry of drugs into the systemic
circulation is within the papillary plexus in the upper
epidermis.
 The process is thus regarded as the end point.

17. FACTORS AFFECTING PERMEATION THROUGH
SKIN:
• Age has an effect on permeation of drugs through skin.
• Blood flow tends to decrease with age and could
reduce transdermal flux.
• Some factors like
Stratum corneum thickness
Presence of hair follicles
Injury or trauma to the skin
Hydration of skin
Effect of humidity and temperature
Chemical exposure

18. Basic components of TDDS:​
 Polymer matrix / drug reservoir
 Drug
 Permeation enhancers

19. Polymer matrix / drug reservoir​
• These control the rate of drug release from the
patches serve as the backbone for TDDS.
• These are prepared by dispersion of drug in solid or
liquid polymer base.
• They should be compatible with drug and other
excipients. examples:
Natural polymers: cellulose derivatives, natural
rubber, starch etc;
Synthetic polymers: polyvinyl alcohol polyvinyl
chloride etc;

20. Drug​:
• Drugs with narrow therapeutic range, extensive first
pass metabolism, short halflife and which require
frequent dosing are used.
Permeation enhancers:
• These are called accelerants, which promote the
permeability of the drug through the stratum corneum.
• They do so by altering the structural components of
stratum corneum I.e, proteins or lipids.
• These include

21. • Surfactants like
• anionic: SLS
• Cationic: dodecyltrimethyl ammonium bromide
• Non ionic : pluforonic F127, pluronic F68.

22. 1. BACKING LAMINATE:
It is the top most layer, which is farthest from the skin.
The function of this layer is to prevent the TDDS from water,
dust, microorganisms.
2. DRUG RESERVOIR:
This layer is present immediately below the backing
layer.
It is sandwiched between the rate controlling membrane and
backing layer. It is made up of homogenous dispersion of drug
molecules which are continuously supplied for the
predetermined functional lifetime of TDDS.

23. The rate of drug release from the drug reservoir is
usually much greater than the amount of drug the skin can
probably absorb so as to ensure constant drug supply to the
circulatory system
3. RATE CONTROLLING POLYMER MEMBRANE :
This layer follows the drug reservoir. The membrane may
be porous or nonporous . It controls the release of drug from
the reservoir.

24. Types of TDDS:
o Membrane permeation controlled TDDS
o Adhesive dispersion TDDS
o Matrix diffusion controlled TDDS
o Micro reservoir type TDDS

25. MEMBRANE PERMEATION CONTROLLED TDDS
EX: for 3 days protection of motion sickness
trasdermscop (scopalamine and transderm nitr(nitroglycerine)) for
once a day medication of angina pectoris.

26. ADHESION DISPERSION TYPE TDDS:
EX: Deponit(nitroglycerine) for once a day medication of angina
pectoris
Verapamil releasing TDDS once a day for hypertension.

27. MATRIX DIFFUSION CONTROLLED TDDS
Nitro Dur (Nitroglycerine) used for once a day
medication of angina pectoris

28. MICRORESERVOIR TYPE TDDS:
EX:Nitro-dur (Nitroglycerin) for once a day treatment of
Angina Pectoris.

29. EVALUATION:
1) Evaluation of adhesives
There are three factors which are considered
a) Peel adhesive properties
b) Tack properties
i. Thumb attack test
ii.Rolling ball test
iii.Quick stick/peel tack test
c) shear strength properties

30. 2. In vitro drug release studies
 Paddle over disc
 The cylinder modified USP basket
 The reciprocating disc
3. In vivo permeation studies
 Permeation of skin for permeation studies by
using
Animal models
Human volunteers
4. cutaneous toxicological evaluation
Contact dermatitis