1. Presented by: DEEPAK B.GADHAVE
Sub: Novel Drug Delivery System
Branch: Pharmaceutics
2. TRANSDERMAL DRUG DELIVERY SYSTEM
Definition:-
It defined as ,distinct dosage form which when applied to the intact skin, delivers the drug
through the skin at a controlled rate to systemic circulation.
Advantages
1. Avoidance of first pass metabolism
2. Avoidance of GI incompatability
3. Longer duration of action
4. Minimizing undesirable side effect
5. Narrow therapeutic window
6. Improving pharmacological & physiological response
7. Avoiding the fluctuation in drug levels
8. Termination of therapy is easy at any point of time
9. Greater patient compliance
10. Self administration
Disadvantages
1. Uneconomic.
2. The delivery system can not be used for those drug requiring high blood flow.
3. Drug or drug formulation may cause skin irritation or sensitization
3. ANATOMY AND PHYSIOLOGY OF THE
SKIN
Human skin comprises of three distinct but mutually dependent tissues:
Epidermis
Dermis
Hypodermis.
Epidermis
Stratum corneum
This is the outermost layer of skin also called as horny layer.
It is approximately 10 mm thick when dry but swells to several times this thickness
when fully hydrated.
It contains 10 to 25 layers of dead, keratinized cells called coenocytes.
It is flexible but relatively impermeable.
The stratum corneum is the principal barrier for penetration of drug.
The lipids are arranged in multiple bilayers. There is sufficient amphiphilic material in
the lipid fraction, such as polar free fatty acids and cholesterol, to maintain a bilayer
form.
4.
5. • Dermis
– Dermis is 3 to 5 mm thick layer and is composed of a matrix of connective
tissue, which contains blood vessels, lymph vessels and nerves.
– The cutaneous blood supply has essential function in regulation of body
temperature.
– It also provides nutrients and oxygen to the skin while removing toxins and
waste products.
– Capillaries reach to within 0.2 mm of skin surface and provide sink conditions
for most molecules penetrating the skin barrier.
• Hypodermis
It is subcutaneous fat tissue support the dermis & epidermis. it serve as fat
storage area. This layer regulate temperature , provide nutrition support &
mechanical protection.it carry blood vessel & nerve to skin & contain sensory
pressure organ.
7. Factor affecting TDDs
Biological factor
1. Skin condition
2. Skin age
3. Blood supply
4. Skin metabolism
5. Species difference
Physicochemical factor
1. Skin hydration
2. Temperature
3. pH
4. Diffusion coefficient
5. Drug concentration
6. Log p
7. Molecular size
8. Methods for Permeation enhancement:
1.CHEMICAL ENHANCEMENT
a. Disruption of the highly ordered of stratum corneum lipid.
b. Interaction with intercellular protein.
c. Improved partition of the drug, coenhance or solvent into the
stratum corneum.
Examples:
1.Solvent:
water, alcohol (ethyl methyl isopropyl),Alkoxide, Dimethyl sulphoxide
(DMSO).
2. pyrrolidones:
2-pyrroliodone, N-methyl pyrrolidone, Laurocapram
3.Ampiphiles;
anionic, nonionic, cationic surfactants.
4.Miscelllaneous:
enzyme, urea, terpenes and sesquiterpenes
12. 4.Electroporation
• Electroporation is also based on the application of a voltage to
the skin.
• In contrast to iontophoresis where a low voltage is applied.
• electroporation requires a large voltage treatment for a short
period of 10 µs to 100 ms.
• Electroporation produces transient hydrophilic pores (aqueous
pathways) across the skin barrier.
These pores allow the passage of macromolecules via a
combination of diffusion, electrophoresis and electroosmosis.
13.
14. 5.Microneedle array
• Microneedles are needles that are 10 to 200 µm
in height and 10 to 50 µm in width.
• They are solid or hollow and are connected to a
reservoir which contains the active principle.
• Needles of approximately with or without centre
hollow channels are placed onto the skin surface
so that they penetrate the stratum corneum and
epidermis without reaching the nerve endings
present in the upper dermis.
15. 6.Pressure waves
Pressure waves are generated by the intense laser radiation and can
permeabilize the stratum corneum and cell membrane; it allows
macromolecules to diffuse stratum corneum and facilitate the
transdermal drug transport through the skin.
The pressure wave is applied for a very short time (100 ns-1μs). It is
thought that the pressure waves form a continuous or hydrophilic
pathway across the skin due to expansion of lacunae domains in the
stratum corneum.
7.Stratum corneum removal
16. TECHNOLOGIES FOR DEVELOPINGTRANSDERMAL
DELIVERY
1.Polymer membrane partition- controlledTDDS
• It has features of both reservoir & matrix dispersion type
drug delivery system.
• The drug reservoir is formed by suspending the drug solid
in an aq. Solution of water soluble polymer.
• The drug suspension is dispersed homogenously in a
Lipophilic polymer, by high shear mechanical agitation to
form thousands of unleachable microspheres of drug.
17.
18. 2. Polymer matrix diffusion-controlledTDDS
• It is formed by homogenously dispersing the drug in a mixture
of hydrophilic – Lipophilic polymer{matrix} & the medicated
polymer is moulded on the medicated disc of defined surface
area & thickness .
• It is then glued over an occlusive base plate consisted of
compartment fabricated using an impermeable plastic backing.
19.
20. 3.Drug resevoir gradient-controlled TDDS
The drug reservoir is encapsulated in a shallow compartment moulded
from a drug impermeable metallic – plastic lamination while the drug
delivery side is covered by controlling polymeric membrane.
21. 4.Microreservoir dissolution- controlledTDDS
• It is the simplified form of membrane moderated drug delivery system
• It is prepared by directly dispensing the drug in an adhesive polymer & then
spreading the medicated adhesive by solvent film casting method over a flat
sheet of drug impermeable metallic or plastic backing membrane, this forms a
thin drug reservoir layer.
22. BASIC COMPONENTS OFTRANSDERMAL DRUG
DELIVERY SYSTEM
1. Polymer matrix
2. Drug substance
3. Penetration enhancer
4. Drug reservoir components
5. Backing membrane
6. Adhesive layer
7. Release liner
23. Evaluation parameter
1. Interaction studies
2. Thickness of patch
3. Weight uniformity
4. Drug content
5. Thumb tack test
6. In-vitro drug release study
7. In-vitro skin permeation studies
8. Skin irritation studies
9. stability studies
24. conclusion
• Delivering medicine to the general circulation through the
skin is seen as a desirable alternative to the oral route.
• Intact skin is not sufficiently permeable to the majority of
drugs, hence permeation enhancement is needed.
• Though chemical enhancers have achieved limited success in
increasing the transdermal transport, they can be employed
together with physical methods to give synergistic action
which would improve the efficacy, safety and convenience of
use, and open up the benefits of the transdermal drug
delivery technology to a much broader range of therapeutic
areas.