TDDS, structure of skin, transdermal system, permeation, formulation processes and evaluation.

1. TRANSDERMAL DRUG DELIVERY
SYSTEM
Bhopal Noble’s College Of Pharmacy, Udaipur
(Rajasthan)
Submitted By:- Saloni Bhandari
M.Pharm. P’ceutics
1st Semester
Guided By:- Dr. Kamal Singh Rathore
Dept. of Pharmaceutics

2.  INTRODUCTION
 ADVANTAGES AND DISADVANTAGES OF TDDS
 STRUCTURE OF SKIN
 PENETRATION THROUGH SKIN
 FACTORS AFFECTING PENETRATION
 PENETRATION ENHANCERS
 BASIC COMPONENTS OF TDDS
 FORMULATION OF TDDS
 EVALUATION
 REFERENCES

3. INTRODUCTION
 Transdermal drug delivery system (TDDS) is topically administered dosage
form in the form of patches which deliver drugs for systemic effects at a
predetermined and controlled rate.
 Transdermal drug delivery system (TDDS) is the dosage forms which deliver a
therapeutically effective amount of drug across a patient’s skin. Transdermal
drug delivery offers controlled release of the drug into the patient, it enables
a steady blood-level profile resulting in reduced systemic side effects and
sometimes, painless and offer multi-day dosing.

4. ADVANTAGES
 Transdermal drug delivery enables the avoidance of gastrointestinal
absorption, with its associated pitfalls of enzymatic and pH associated
deactivation.
 This method also allows for reduced pharmacological dosaging due to
the shortened metabolization pathway of the transdermal route versus
the gastrointestinal pathway.
 The simplified medication regimen leads to improved patient
compliance and reduced inter & intra – patient variability.
 Self administration is possible with these systems.
 The drug input can be terminated at any point of time by removing
transdermal patch.

5. DISADVANTAGES OR LIMITATIONS
 The drug that requires high blood levels cannot be administered and
may even cause irritation or sensitization of the skin
 Only relatively potent drugs are suitable candidates for TDDS
because of the natural limits of drug entry imposed by the skin’s
impermeability.
 High cost of the product is also a major drawback for the wide
acceptance of this product
 Contact dermatitis is another drawback reported in TDDS
 Barrier function of skin varies from site to site during application in
same person.

7. SKIN STRUCTURE
 There are 3 prominent layers of the skin
1. Epidermis
2. Dermis
3. Subcutaneous layer

8. 1. EPIDERMIS
 Epidermis is 0.1-0.2mm thick and tightly filled with cells in which
epidermal keratinocytes constitutes 90% of epidermal cells.
 epidermal keratinocytes are divided into 4 layers:
i. Stratum corneum – corneocyte cells
ii. Granular layer – granular cells
iii. Spinous layer – spinous cells
iv. Basal layer – basal cells
 Other cells present on epidermis are melanocytes and Langerhan cells.
 Keratinazation is the differentiation of basal cells to keratin filled
corneocytes. It is a continuous process and causes renewal of epidermis
called as epidermal turnover.

9. Stratum Corneum:-
 It forms the outermost layer of the epidermis and water content is
around 20%. There are 18-20 such layers of corneocytes in stratum
corneum which are attached to each other by corneodesmosomes.
 It is responsible for barrier function of skin.
 Removal of this layer results in increased penetration and water loss.

10. 2. DERMIS
 Dermis is made up of network of collagen fibers responsible for elastic
properties of the skin.
 It has sweat gland and sebaceous glands.
3. SUBCUTANEOUS
 This is the sheet of the fat containing aerolar tissues known as
superficial fascia attaching the dermis to the underlying structures.

11. PENETRATION THROUGH SKIN
 Skin penetration occurs by following routes-
a. Tans epidermal absorption
b. Trans follicular absorption
c. Clearance by local circulation
Pathways of permeation through skin

12. a. Trans epidermal absorption
 Stratum corneum is main resistance for absorption through this route.
 Penetration involves partitioning of drug into the stratum corneum.
 It depends on o/w distribution tendencies of the drug. Lipophillic drug
penetrates and diffuse much easily.
b. Trans follicular absorption
 Drug through this route passes from corneocytes which has highly
hydrated keratin creating hydrophilic pathway.

13. Factors Affecting Penetration
 Blood flow
 Age
 Thickness of stratum corneum
 Hair follicles
 Injury or trauma to the skin
 Skin hydration
 Humidity and temperature
 Use of certain drugs

14. BASIC COMPONENTS OF TDDS
1. Polymer matrix-
It releases the drug from the device.
a) Molecular weight of polymer should be such that drug diffuses
properly and gets released through it.
b) It should be stable and non reactive with the drug.
c) It should be non toxic.
Natural polymers: Cellulose derivatives, shellac, zein, waxes, natural
rubber starch, gums etc.

15. Synthetic elastomers: poly butadiene, hydrin rubber, butyl rubber etc.
Semi synthetic polymers: PVC, PVP, poly propylene etc.
2. Drug-
a) Physicochemical properties; non ionic, low molecular weight, low
melting point
b) Biological properties; short t1/2, non irritant etc.
3. Penetration enhancers-
These are the substances which promotes skin penetration by altering the
skin as a barrier to the flux of the desired drug penetrant.

16. J = D dc/dx
D= diffusion coefficient
c = concentration of diffusing drug
x = spatial coordinate
a) Solvents
b) Surfactants
i. Anionic- SLS, dicotyl sulphosuccinate
ii. Non anionic- pluronic F127, F67
iii. Bile salts- sodium deoxycholate, sodium taurocholate
c) Binary systems- PG, oleic acid
d) Miscellaneous- urea, calcium thioglycolate

17. FORMULATION OF TDDS
1. Membrane permeation
2. Adhesive dispersion
3. Matrix diffusion
4. Micro reservoir type or micro sealed dissolution
5. Proplastic type
6. Transdermal delivery of macromolecules

18. 1. Membrane permeation
 Drug reservoir is completely encapsulated in a shallow compartment
molded from a drug-impermeable metallic plastic laminate and a rate
controlling polymeric membrane which may be micro porous or non
porous.
 The rate of drug release can be altered by varying polymer composition,
permeability coefficient, and adhesive thickness.
 Examples- nitroglycerin releasing transdermal system for once a day
medication in angina pectoris.
scopolamine releasing TDDS for 72hrs. Prophylaxis of motion sickness.

19. 2. Adhesive dispersion
 Drug reservoir is formulated by directly dispersing drug into a adhesive
polymer and then spreading the medicated adhesive by hot melt on a flat
sheet of drug impermeable plastic laminate to form a thin drug reservoir.
 Example- isosorbide dinitrate releasing TDDS in angina pectoris.

20. 3. Matrix diffusion
 It is prepared by homogenously dispersing drug particles with a liquid
polymer followed by cross linking of the polymer chains.
 It is then pasted on the an occlusive base plate in a compartment made
from drug impermeable plastic backing, adhesive polymer is then spread
to form a strip of adhesive rim around the medicated disc.

21. 4. Micro sealed dissolution
 It is combination of reservoir and matrix diffusion type drug delivery
system.
 Drug reservoir is formed by suspending the drug solids in an aqueous
solution of water soluble liquid polymer and then dispersing the drug
suspension homogenously in a lipophillic polymer such as silicone
elastomers by high dispersion technique.

22. 5. Proplastic type systems
 It is based on concept of water coagulation of cellulose triacetate
solution in organic acids at low temperature.
 The coagulation is performed under controlled conditions.
6. Transdermal delivery of macromolecules
 Macromolecules like hormones, interferons, peptides etc can be delivered by
use of certain devices. These devices are either based on silicone elastomers
or ethylene vinyl acetate copolymers.
 Both the devices utilize concept that the matrix must have channels to
facilitate the release of macromolecules.

23. EVALUATION OF TDDS
1. In vitro release evaluation:-
 In this study, skin(hairless) of mouse is used.
 Excised skin is mounted on skin permeation cells.
 In vitro release system should be designed in such a manner that intrinsic
rate of release or permeation can be accurately determined.
 Valia-Chein cells, Ghannam-Chein membrane permeation cells, Jhawer-
Lord rotating disc cells, and Keshary- Chein cells.

24. 2. In vivo evaluation:-
A. Animal models-
 Rhesus monkey is the most acceptable animal model for this evaluation.
 Standard radio tracer methodology is used.
 Application site is generally forearm or abdomen because less hairs are
present.
B. Human models-
 Involves determination of cutaneous absorption by an indirect method of
measuring radioactivity in excreta following topical application of the labeled
drug.

25.  The % of drug absorbed transdermally is given by-
3. Evaluation of adhesives:-
a. Peel adhesive properties
b. Tack properties
i. Quick stick (peel tack) properties
ii. Probe tack test
c. Shear strength properties

26. REFERENCES
 Y.W. Chein, Novel Drug Deliver Systems, 2nd Edition, Revised And Expanded,
1992.
 N.K. Jain, Controlled And Novel Drug Delivery, CBS Publisher And
Distributers, New Delhi, 1st Edition, 1997.
 Mechanism Of Transdermal Drug Deliver System By Y.W. Chein Marcel
Dekker, Inc., New York.
 www.pharmatutour.com
 Seminar On Transdermal Drug Delivery System By P.Chakradhar.
 www.slideshare.net
 www.google.com