Transdermal drug delivery System

1. TRANSDERMAL DRUG DELIVERY SYSTEM
(TDDS)
Presented By;
Mr. Trilok D. Shahare
M.Pharm, I Semester
Department of Pharmaceutics
D. B. C. O. P. Besa, Nagpur
Guided By;
Dr. N. M. Mahajan
Department of pharmaceutics
D. B. C. O. P. Besa, Nagpur
1

2. CONTENTS
2
1 Introduction
2 Advantages
3 Disadvantages
4 Skin And Structure Of Skin
5 Function Of Skin
6 Factor Affecting TDDS
7 Type/Technology For Development Of TDDS
8 Evaluation Parameters
9 Reference

3. INTRODUCTION
- Transdermal drug delivery system (TDDS), also known as
patches.
- Transdermal is a rout of administration wherein active
ingredient are delivered across the skin for systemic
distribution.
- It is a dosage forms designed to deliver a therapeutically
effective amount of drug across a patient’s skin.
- Transdermal system, was approved by FDA in 1979 for the
prevention of nausea and vomiting.
3

4. 4

5. General Patches….
Backing – protect the patch from environment.
Membrane – Control the release of drug.
Adhesive – Adher the component of patch together adhere the patch release.
Liner- Protect the patch during storage
5

6. TDDS offers…
Iv Oral TDDS
Reduced first-pass
effect.
Yes No Yes
Constant drug level Yes No* Yes
Self-administration No Yes Yes
Unrestricted patient
activity
No Yes Yes
6

7. Advantages :
 Easy to use.
 Self medication is possible.
 Avoidance of first pass metabolism, Salivary
metabolism and intestinal metabolism.
 Avoidance of gastrointestinal incompatibility.
 No interaction with food or drink, and enzyme.
 Prolong duration of action (ranging from few hrs. to one
week)
7

8. Disadvantages :
 Local irritation at site of application.
 Allergic reaction.
 Difficult in long time adherence.
 Cannot deliver ionic drug.
 The adhesive used may not adhere well to all type of
skin.
 Difficult to administer large dose.
8

9. About Skin :
 Skin is the largest organ in the body.
 Primary site of delivery.
 It consist of 6% of total body weight (e.g 50kg person-3kg of
skin).
 Skin pH acidic 4.2-5.6 pH.
 The skin contains a protein called keratin which is also in
found in hair and nails.
 Each 5 square cm of skin may have up to 600 sweat gland.
9

10. Structure of skin :
• I. Epidermis
Stratum corneum (Horny cell layer)
Stratum granulosum ( Granular Layer)
 Stratum spinosum (Prickly layer)
 Stratum basale
• II. Dermis
• III. Hypodermis or Subcutaneous layer
10

11. I. Epidermis :
 Outer most layer
 Composed of stratified squamous
epithelial cell.
 Epidermis layer provides a
barrier to infection from
environmental pathogen.
 And regulate amount of water
release from the body.
11

12. a) Stratum corneum :
 This is the outermost layer of skin called as horny layer with
approximately 10 mm thickness.
 Which comprises of 15–30 sheet of non-viable, but
biochemically active corneocytes.
b) Stratum granulosum : is the middle layer of epidermis and
chiefly involved in providing waterproof function. It also
contributes keratinization process of the skin.
c) Stratum spinosum : composed of 8–10 sheet of keratinocytes
with limited dividing capacity.
12

13. c) Stratum spinosum : composed of 8–10 sheet of keratinocytes
with limited dividing capacity and is also a seat for langerhan’s cell
d) Stratum basal : is a hub for maturing/aging keratinocytes,
melanocytes, Merkel cells referred as a receptor cells.
13

14. II. Dermis
 Dermis is a layer of skin between the epidermis and subcutaneous tissues.
 It’s major role to provide the much needed responsible for the tensile
strength of skin.
 It is a 3 to 5 mm thick layer, composed of matrix connective tissue which
contains blood vessels, lymph vessels and nerves.
 In which mechanoreceptors that provides the sense of touch and heat.
 Primarily regulates temp. and also provide nutrients and oxygen to the skin.
 Major components include :
I. Hair follicles
II. Connective tissue
III. Sweat gland
IV. Blood vessels 14

15. III) Subcutaneous layer :
 Subcutaneous tissue, which also known as the hypodermis,
hypoderm is the inner most layer of skin.
 It’s is made up of fat and connective tissues that house larger
blood vessels and nerves.
 Subcutaneous tissue act as an insulator and regulate body
temperature.
 The subcutaneous tissue layer its function to protect the muscle
and bones.
 For transdermal drug delivery drug has to penetrate through all
these three layers and reach into systemic circulation.
15

16. Function of Skin :
 Protection
 Sensation e.g. heat, cold, touch, pressure, vibration, tissue injury.
 Regulation of body temperature
 Formation of vitamin D – by the action of UV on certain parts of skin.
 Absorption
 Excretion – sweat.
16

17. Fig . Diagram showing absorption of molecules through skin layers
17

18. 1.patch
2.Layer of patch
3.Release of drug from patch 18

19. MECHANISM OF ABSORPTION
(through skin)
Mechanism involved is passive diffusion.
This can be expressed by FICK’s steady state diffusion,
J = KD/h (co – ci )
Where,
• J = flux per unit area,
• K = stratum corneum –formulation partition coefficient of
drug,
• D = diffusion coefficient in the stratum corneum of path length ‘h’; Co
= Conc. of drug applied to skin & ci = conc. inside the skin.
19

20. Factors influencing TDDS
1. Biological Factors
2. Physicochemical factors
3. Environmental factor
20

21. 1.Biological factor :
1 Skin condition
2 Skin age
3 Blood supply
4 Regional skin site
5 Skin metabolism
6 Species differences
21

22. 2.Physicochemical factor :
1 Skin hydration
2 Temp. and pH
3 Diffusion coefficient
4 Drug concentration
5 Partition coefficient
6 Molecular size and shape
22

23. 3. Environmental factor :
1 Sunlight
2 Cold season
3 Air pollution
4 Effect of heat on transdermal
patch
23

24. Types / Technologies for developing of TDDS :
 1. Polymers Membrane Partition-Controlled TDDS
 2. Polymer Matrix Diffusion-Controlled TDDS
 3. Drug Reservoir Gradient-Controlled TDDS
 4. Micro-reservoir Dissolution-Controlled TDDS
24

25. 1. Polymers Membrane Partition-Controlled TDDS
 In this type of systems, the drug reservoir is sandwiched between a drug
impermeable metallic-plastic lamination and rate controlling polymeric
membrane.
25

26. Drug mixed with
polymeric solution
Containing unleachable
viscous fluid
That forms
paste like
suspension
Upper coat- drug impermeable metallic-plastic lamination
Middle coat- rate controlling membrane
Lower coat- thin adhesive polymer layer
Molding as TDD System
Packaging machinery
Primary packaging
Secondary packaging
26

27. The intrinsic drug release from this type of TDDS is defined by :
𝑑𝑄
𝑑𝑡
=
𝐾𝑚/𝑟
𝐾𝑚/𝑟
𝐾𝑎/𝑚𝐷𝑎𝐷𝑚
𝐷𝑚ℎ𝑎+𝐾𝑎/𝑚𝐷𝑎ℎ𝑚
𝐶𝑟
Where,
Cr – Drug conc. in reservoir compartment.
Km/r & Ka/m – partition coefficient for the interfacial partitioning of drug
from reservoir to membrane & membrane to adhesive respectively.
Da & Dm – Diffusion coefficient in rate control membrane & adhesive
layer.
ha & hm – Thickness of rate controlled membrane and adhesive layer.
27

28. Examples :
1.Transderm-nitro for angina pectoris.
2. Transderm - scop for motion sickness.
28

29. 2. Polymer Matrix Diffusion-Controlled TDDS :
Solid drug dispersed in
hydrophilic/hydrophobic
polymer matrix
Medicated polymer is
molded into medicated disc
Plastic backing coat
provided
Polymer disc mounted
on occlusive base
plate
Instead of adhesive
polymer strip adhesive
rim is used
Polymer matrix diffusion
TDDS ready
Medicated
polymer
Medicated polymer
disc
29

30. Fig : Cross-section view of polymer matrix diffusion-controlled TDDS
30

31. The rate of drug release from this type of TDDS is defined.
Where,
Ld – Drug loading dose initially dispersed in polymer matrix
Cp – Solubility of drug in polymer matrix
Dp – Diffusivity of drug in polymer matrix
example :
Nitro-dur II system for angina pectoris
31

32. 3. Drug Reservoir Gradient-Controlled TDDS
Drug-impermeable laminate
Drug
Reservoir
Gradient
Adhesive layer
Drug molecules
32

33. Drug release from this type can be expressed by-
𝑑𝑄
𝑑𝑡
=
𝐾𝑎/𝑟𝐷𝑎
ℎ𝑎(𝑡)
𝐿𝑑 (ℎ𝑎)
Where,
Ka/r – Partition coefficient for interfacial partitioning of drug from the
reservoir layer to adhesive layer.
 Example :
Verapamil for Hypertension
33

34. 4. Microreservoir Dissolution-Controlled TDDS
 This is combination of reservoir and matrix diffusion type of DDS.
Microreservoir dissolution controlled patch is ready
This medication disc positioned at the centered and surrounded by an
adhesive rim
Drug suspension dispersed into lipophilic polymer to form unleachable
microspheres of drug reservoir
Solid drug suspended in aq. Solution of water soluble polymer
Drug suspension
By polymeric cross linkingUnstable dispersion converted to stable
34

35. fig : Microreservoir dissolution-controlled TDDS
35

36. • The rate of drug release from this system is defined by :
where,
Kl – liquid compartment to polymer matrix
Km – polymer matrix to polymer compartment
Kp – polymer coating membrane
Dl – liquid compartment
Dp – polymer coating membrane
Ds – elution solution
Sl – liquid compartment
Sp – polymer matrix 36

37. hl – liquid layer surround drug particles.
hp – polymer membrane coating around polymer matrix
hd – hydrodynamic diffusion layer surrounding the polymer coating
membrane.
Examples :
Nitro-disc for angina pectoris.
37

38. EVALUATION OF TDDS
1) Interaction Studies
2) Thickness of the Patch
3) Weight Uniformity
4) Folding Endurance
5) % Moisture Content
6) % Moisture Uptake
7) Drug Content
8) Polariscope Examination
38

39. 5) Percent moisture content
formula :
(𝑖𝑛𝑖𝑡𝑖𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡 − 𝑓𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
𝑓𝑖𝑛𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡
× 100
39
9) Polariscope
apparatus

40. REFERENCE :
 Novel drug delivery systems, 2nd edition, by Y.W. Chien
page no : 301 – 375.
 Tanwar, Transdermal drug delivery system : A review,
International Science and Research 2016, 7(6) : 2274-
2290.
 Novel drug delivery system, Nirali Prakashan, by Dr.
Dheeraj T. Baviskar, page no : 6.1 to 6.36
40

41. FOR YOUR SUPPORT, HELP AND PATIENCE…
41

42. 42