transdermal route drug delivery and their advantages and disadvantages

1. Transdermal drug delivery system
LaraibTariq
PharmD
4th semester

2. Contents:
• Definition.
• Skin.
• Permeation through skin.
• Factor affecting permeation through skin.
• Properties of drug for TDDS.
• Basic component of TDDS.
• Preparation of TDDS.
• Advantage.
• Disadvantage.

3. Definition:
 Transdermal drug delivery system are defined as self
contained discrete dosage form which when applied to intact
skin deliver the drugs, through the skin, at a controlled rate to
systemic circulation.
 Transdermal drug delivery system are also known as
Transdermal patches.

4. skin:
 The skin is the largest organ of the human body which
receives about one third of the blood circulation through the
body.
 It serve as a permeability barrier against the transdermal
absorption of various chemical and biological agents.
 Layers of the Skin:
 Epidermis.
 Dermis.
 Subcutaneous.

5. Layers of Skin:

6. Mechanisms involve in Drug Permeation
through Skin:
 The permeation through skin occurs by the following routes:
1. Transepidermal absorption
2. Transfollicular (shunt pathway absorption)
3. Transcellular and Intercellular route

7. Permeation Through Skin
 Transepidermal Absorption:
 The outer most layer of the skin is stratum corneum, is the
primary layer through which most drug molecules penetrate
the skin.
 It consists of layer of compressed, keratin-filled corneocytes,
anchored in a lipid matrix.
 This arrangement of the corneocytes and lipids makes the
skin about a thousand times less permeable to water.
 Lipophillic drug concentrate diffuse with relative ease.

8.  Transfollicular Absorption:
 The transappendageal route are also known as shunt routes, and
include permeation through the sweat glands and across the hair
follicles with their associated sebaceous gland.
 More lipophilic drugs cross this section due to the lipophilic nature
of sebum.

9.  Transcellular route/ Intracellular route:
 Drug delivery through this route passes from corneocytes which has
highly hydrated keratin creating hydrophilic pathway.
 The drug passes through the corneocytes of stratum corneum.
 Hydrophilic drugs pass through intracellular pathways.
 Intercellular route:
 In intercellular pathway drug diffuses through the continuous lipid
matrix present between the cells.
 Lipophilic drugs traverse the stratum corneum via the intercellular
route.

10. Factors Affecting Permeation through Skin:
 Age has an effect on the permeation of drugs through the skin.
 Blood flow (dermal clearance of the molecule transversing the tissue) tends to
decrease with age and could reduce transdermal flux.
 The other factors that affect the permeation of the drug through the skin are:
 The stratum corneum thickness.
 Presence of hair follicles.
 Injury or trauma to the skin.
 Hydration of the skin.
 Effect of humidity and temperature
 Chemical exposure
 Chronic use of certain drugs.
 Grooming.
 Skin temperature.

11. Basic Components of Transdermal Drug
Delivery Systems:
 The components of transdermal devices include:
1. Polymer matrix or matrices
2. The drug
3. Permeation enhancers
4. Other excipients

12. Drug:
 For successful development of a transdermal drug delivery, the following are the
desirable properties of a drug for transdermal drug delivery.
1. Physiochemical properties.
2. Biological properties.

13. Physiochemical Properties:
 It is generally accepted that the best drug candidate for passive adhesive
Transdermal patches must be:
 Non-ionic
 Low molecular weight
 Adequate solubility in oil and water.
 Low melting point (less than 200° C)
 Potent (dose less than 50mg per day, and ideally less than 10 mg per day).

14. Biological Properties:
 The drug should be potent with a daily dose of order of a few mg/day.
 The half life of the drug should be short.
 The drug must not induce a cutaneous irritant or allergic response.
 Drugs degraded in the GIT or inactivated by the hepatic first pass are suitable
candidates for transdermal drug delivery.

15. Polymers matrix :
 The polymer controls the release of the drug from the device.
 Ideal properties of polymers for transdermal drug delivery system:
 The polymer should be stable, non-reactive with the drug, easily manufactured and
fabricated in to the desired product; and inexpensive.
 The polymer and its degradation products must be non-toxic.
 The mechanical properties of the polymer should not deteriorate excessively when
large amounts of active agent are incorporated in to it.
 Possible polymers for Transdermal devices are;
1. Natural polymer:
2. Synthetic polymer:

17. Permission enhancers:
 Following are the properties of permeation enhancers.
1. The material should be pharmacologically inert.
2. It should be non-toxic, non-irritating, and non-allergenic.
3. The action should be immediate and the effects should be suitable and
predictable.
4. The enhancer should not cause loss of body fluids, electrolytes or other
endogenous material.
5. It should be compatible with all drugs and excipients.
6. It should be odourless, tasteless, and colorless

18. Classification of permeation enhancers:
 Following are the different permeation
enhancers.
• Solvents.
• Surfactants.
1. anionic surfactant: sodium lauryl sulfate.
2. Non ionic surfactant: pluronic F68
3. Bile salts: sodium deoxycholate.
• Miscellaneous chemicals: urea, calcium
thioglycholate.

19. Other excipients:
 Adhesives:
The adhesive should satisfy the following criteria:
1. Do not irritate or sensitize the skin.
2. Adhere to the skin during the dosing interval.
3. It should be remove easily.
4. It should be physically and chemically compatible with the drug, excipients and
enhancers.
5. Permeation of drug should not be affected.

20. Formulation of TDDS:
 Types: following are the formulation of TDDS.
1. Polymer membrane permeation controlled TDDS.
2. Adhesive diffusion controlled TDDS .
3. Matrix diffusion controlled TDDS.
4. Microreservior controlled TDDS.

21. Polymer membrane permeation controlled TDDS:
 The drug reservoir is totally encapsulated in a shallow compartment moulded 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 from this type of TDDS can be tailored by varying the
composition of polymer, permeability coefficient, thickness of rate limiting
membrane and adhesive.
Example:
• Nitroglycerine releasing Transdermal system for once a day medication in angina
pectoris.
• Scopolamine releasing Transdermal system for 72 hrs. Prophylaxis of motion sickness.

23. Adhesive diffusion controlled TDDS:
 The drug reservoir is formulated by directly dispersing drug in an adhesive polymer
and then spreading the medicated adhesive polymer on to flat sheet of drug
impermeable metallic plasting backing to form a thin drug reservoir layer.
 Example: Isosorbide dinitrate-releasing Transdermal releasing system for
once a day medication of angina pectoris.

25. Matrix diffusion control system:
• It is prepared by homogenously despring the drug particles with a liquid polymer or
highly viscous base polymer followed by cross linking of polymer chains or
homogenously blending the drug solids with a rubbery polymer at elevated
temperature.
• It can also be prepared by dissolving the drug and polymer in a common solvent
followed by solvent evaporation in a mould at a elevated temperature or in a
vaccum. It is then pasted onto occlusive base plate in compartment fabricated from
drug impermeable plastic backing, the adhesive polymer is then spread along
circumference to form a strip of adhesive rim around medicated disc.
• Example: Nitroglycerine releasing Transdermal system (Nitro Dur & Nitro Dur II) at
daily dose of 0.5 g/cm2 for therapy of angina pectoris.

27. Microreservior controlled TDDS:
 This drug delivery system is combination of reservoir and matrix diffusion type
system.
 The drug reservoir is formed by first suspending the drug in aqueous solution of
water soluble polymer and then dispersing the drug suspension homogenously in
lipophilic polymer such as silicone elastomers by high dispersion technique.
 Example: Nitroglycerine-releasing Transdermal system (Nitro disc) for once a day
therapy of angina pectoris.

30. Disadvantage:

31. Transdermal drug delivery system products: