Transdermal drug delivery systems (TDDS) deliver drugs through the skin and into systemic circulation at a controlled rate. TDDS provide advantages like avoidance of first-pass metabolism and allowing controlled drug levels. The skin is a barrier, so permeation involves partitioning into the stratum corneum then diffusion across layers. Factors like a drug's physicochemical properties, the delivery system composition, and skin conditions influence permeation kinetics. TDDS have components like polymer matrices, drugs, and permeation enhancers. They are evaluated for properties such as adhesive peel adhesion to ensure removal does not damage skin.

1. TRANSDERMAL DRUG DELIVERY
SYSTEM
PRESENTED BY
gandhi sonam m.

2. TRANSDERMAL DRUG DELIVERY
SYSTEM
DEFINITION:
Transdermal therapeutic system are defined as self-
contained discrete dosage form which when applied to the intact
skin deliver the drugs, through the skin, at a controlled rate to the
systemic circulation.
OR
Transdermal drug delivery systems (TDDS) are systems that
utilize skin as a site for continuous drug administration into the
systemic circulation

3. ADVANTAGES
Transdermal delivery can increase the therapeutic value of many
drugs by avoiding specification due to hepatic “First pass” effect,
formation of metabolites that causes side effects, short half life
necessitating frequent dosing etc.
Self administration is possible with these system.
The drug input can be terminated at any point of time by removing
transdermal patch.
Allows effective use of drugs with short biological half-life
Allow administration of drugs with narrow therapeutic window
Provides controlled plasma level of very potent drugs
Drug input can be promptly interrupted when toxicity occurs

4. DISADVANTAGES:
The barrier function of the skin changes from one site to another on the
same person or person to person and with age.
Drug that require high blood levels cannot be administered
Adhesive may not adhere well to all types of skin
Drug or drug formulation may cause skin irritation or sensitization
Uncomfortable to wear
May not be economical.

6. Skin as site for drug administration
 epidermis-
 Dermis
 Hypodermis

7. PERMEATION THROUGH SKIN
. mechanism of permeation can involve passage through the epidermis
The
itself (transepidermal absorption) or diffusion shunts.
TRANSEPIDRERMAL ABSORPTION
It is now believe that the transdermal pathway is principally
responsible for diffusion across the skin. The main resistance encountered
along this pathway arises in the stratum corneum. Permeation by the
transepidermal route first involves partitioning into the stratum
corneum. Diffusion then takes place across this tissue.

8. Transdermal permeation (percutaneous absorption):
• The passage of substance from the outside of the skin
through its various layers into the bloodstream.
• Transdermal permeation
Drug
Particles

9. Kinetics of transdermal permeation
Knowledge of skin permeation kinetics is vital to the successful
development of transdermal therapeutic systems. Transdermal
permeation of a drug involves the following steps.
Sorption by stratum corneum,
Penetration of drug through viable epidermis,
Uptake of the drug by capillary network in the dermal papillary layer.

10. Fundamentals of skin permeation
Rate of permeation, dQ/dt, across a skin can be
expressed as:
dQ / dt = Ps (Cd - Cr)
where
dQ/dt – Rate of permeation
Ps – Permeability coefficient
Cd – Concentration in donor compartment
Cr – Concentration in receptor
compartment

11. .
FACTORS AFFECTING TRANSDERMAL
PERMEABILITY
The principle transport mechanism across mammalian skin is by
passive diffusion. The factors influencing and having differences in
transdermal permeability of the stratum corneum can be classified into 3
major category.
1.Physico-chemical properties of penetrants (drug)
2.Physico-chemical properties of drug delivery system.
1.Physiological and pathological condition of skin.

12. Physico-chemical properties of penetrant molecule (drug) :
Partition coefficient: Drugs possessing both water and lipid solubility
are favouraly absorbed through skin. Transdermal permeability
coefficient shows a linear dependency on partition coefficient. A liped /
water partition of 1 or greater is generally required for optimal
transdermal permeability.
pH condition: The extent of dissociation in case of ionic drugs and
their transdermal permeability depends on the pH condition of skin
surface as well as of the drug delivery system. In case of ephedrine and
scopolamine, the transdermal flux of the drug increases with
increasing pH up to approximately 1.2 higher than their respective
pKa values.

13. Physico-chemical properties of Drug Delivery System:
Release Characteristics:
The release characteristics of drug from delivery system can largely
affect the transdermal permeation of drug molecules.
The release of drug from the delivery vehicle depends on its
affinity to the vehicle. The transdermal permeation rate increase as the
drug releases rate from the drug delivery system increases.

14. Composition of drug delivery system: (vehicle)
Composition may not affect the rate of drug release, but affect the
permeability of the stratum corneum by means of hydration, mixing
with skin lipids.
Eg: Salicylic acid and its methyesters, methyl salicylate is more lipophilic
then its parent acid and when applied to skin from fatty vehicle, they
methyl salicylate yielded a higher percutaneous absorption then salicylic
acid.
Incorporation of transdermal permeation:
Like dymethyl sulphoxide, acetone, propylene glycol,
tetradihydrofurfuryl alcohol, dimethyl sulphoxide etc in typical
formulation increases drug permeation.

15. Physiological & pathological condition of skin:
Presence of hair follicle: Absorption is rapid where more hair follicles
present eg: scalp.
Thickness of stratum corneum: Absorption is low from region as foot and
palm.
Trauma: cut inflammation, rashes, mild burn where stratum corneum is
destroyed, promote drug absorption.
Hydration of skin: Soaking skin in H2O, plastic film, dressing promote
hydration of skin and drug absorption increase.
Age: Aged skin more prone to allergy and irritant effect, of topically
contacted drug infant particularly concerned.

16. Grooming: the frequency and vigor with which one bathes and
type of soap that is used also contributes variability in drug
absorption.
Chronic use of certain drug: long term use of keratolytics like
salicylic acid results in increased drug penetration.
Skin temperature: increase temperature increase absorption
because of increase vasodilatation of skin vessels eg: 10 fold
increase skin permeation of aspirin and glucostroids was noticed
when the environmental temperature increase from 10-51 C.

17. BASIC COMPONENTS OF TRANSDERMAL DRUG
DELIVERY SYSTEMS:
The components of transdermal devices include:
Polymer matrix or matrices
The drug
Permeation enhancers
Other excipients

18. Polymer matrix or matrices
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 into the desired product;
and inexpensive.
The polymer and its degradation products must be non-toxic
or non-antagonistic to the host.
The mechanical properties of the polymer should not
deteriorate excessively when large amounts of active agent
are incorporated into it.

19. Possible useful polymers for transdermal devices are:
Natural polymers:
Synthetic Elastomers:
Synthetic Polymers:

20. Drug
Desired properties of drug for transdermal drug delivery systems are
Physicochemical properties,biological properities
penetration enhancer are:
The material should be pharmacologically inert.
It should be non-toxic, non-irritating and non-
allergenic.
The action should be immediate and the effect should
be suitable and predictable.

21. Upon removal of the material, the skin should immediately and
fully recover its normal barrier property.
The enhancer should not cause loss of body fluids, electrolytes or
other endogenous materials.
It should be compatible with all drugs and excipients.
The substance should be a good solvent for drugs.
The material should be cosmetically acceptable (good spread ability
and skin ‘feel’).
The chemical should formulate into all the variety of preparations
used topically.
It should be odourless, tasteless, colourless and inexpensive

22. Solvents:
Water is well-recognized in the dermatological field that
promotes the topical pharmacological effect of a number drugs (e.g.,
steroids). The mechanism of action is suggested to involve hydration of
keratin and intracellular lipids however, recent infrared and x-ray
experiments show that increasing the hydration of stratum corneum
does not increase lipid chain disorder or the interlamellar spacing.
Alcohol and ethanol, in particular, have been proposed as effective
permeation enhancers.
Examples:
Acetamide and derivatives, acetone, dimethyl acetamide, dimethyl
formamide, ethanol, ethanol / glycerol, polyethylene glycon, span-20,
tween-80, etc.

23. electrode
Passig
current
patch
Formationof
microchanne
l
Release of
drug

24. Evaluation of TDDS

25. Evaluation of adhesive:
Pressure sensitive adhesives are evaluated for following
properties.
Peel adhesion properties:-
Peel adhesion is the force required to remove an adhesive coating
from a test substrate. It is important in transdermal device because the
adhesive should not damage the skin on removal. peel adhesion
properties are affected by the molecules weight of the adhesive polymer,
the type and amount of additives, and polymer composition.

26. • It is tested by measuring the
force required to pull a single
coated tape, applied to a
substrate at a 1800C angle.
• No residue on the substrate
indicates adhesive failure which
is desirable for transdermal
devices.
• Remnants on all substrate
indicates ‘cohesive failure’
signifying a deficit of cohesive
strength in the coating.

27. Shear Strength properties:
• Shear strength is the
measurement of cohesive
strength of an adhesive polymer.
Adequate strength means device
will not slip on application and
will not leave any residue on
removal. It is determined by
measuring the time it takes to
pull an adhesive coated tape off a
stainless steel plate, when a
specified wt is hung from the
tape which pulls the tape in a
direction parallel to the plate.

28. In vitro drug release evaluation:
1.In vitro permeation kinetics studies can be performed on hairless
mouse skin or human cadaver skin by using franz diffusion cell or two
reservoir diffusion cell.
2.In two reservoir diffusion cells, sink conditions can be maintained.
3.The permeation of nitroglycerins across human cadaver and hairless
mouse skin from different Transdermal Drug Delivery therapeutic
system was compared for their kinetics.
4.It was noted that the rates of skin permeation generated from the
excised skins of hairless mouse agree fairly with the date obtained from
human cadaver skin, suggesting that hairless mouse skin could be an
acceptable animal modes for human skin permeation kinetics studies.

29. Franz diffusion cell
• Franz diffusion cell and the
keshary-chien (K-C) cell . the
most widely used of these are
the franz diffusion cell and the
k-c cell . The K-C Diffusion has
an effective receptor volume of
12ml and skin surface area
3.14cm2 .The receptor solution is
stirred by a star-head magnate
rotating at a constant speed of
600 rpm .

30. In-vivo evaluation:
AnimAl model:
In vivo animal models are preferred because considerable time and
resource are required to carry out studies in human. Some of the animal
are used to in vivo studies are mouse, rat, guinea pig, rabbit, hairless
mouse, hairless rat, hairless dog, cat, dog, miniature pig, pig, horse, goat,
squirrel, monkey. Etc.

31. Human model:
The final stage in the development of transdermal device involves the
collection of pharmacokinetic and pharmacodynamic data following
application of the device to human volunteers.
Determination of absorption following topical administration requires
the investigator to know the amount of radioactivity retained in the
body, or excreted by routs not monitored (assayed).
This necessitates measurement of elimination following parenteral
(ideally i.v.) administration of the compound
The percentage of dose absorbed transdermally is then calculated as
% dose absorbed =Total radioactivity excreted after topical administration
Total radioactivity excreted after I.v administration .100

32. ConClusion
TDDS offers number of advantages to patient
TDDS offers scope for companies in terms of revenue
Importantly, newer advances in transdermal technology
including microporation provides a means for delivering
proteins and peptides

34. References
• B. Decadt and A.K. Siriwardena, "Radiofrequency Ablation of
Liver Tumors: A Systematic Review," Lancet Oncol.5 (9),
550–560 (2004).
• A. Hines-Peralta and S.N. Goldberg, "Review of
Radiofrequency Ablation for Renal Cell Carcinoma," Clin.
Cancer Res. 10 , 6328S–6334S (2004).
• S. Nahum Goldberg, "Radiofrequency Tumor Ablation:
Principles and Techniques," Eur. J. Ultrasound 13 (2), 129–
147 (2001).
• L. Solbiati et al., "Radiofrequency Thermal Ablation of
Hepatic Metastases," Eur. J. Ultrasound, 13 (2), 149–158
(2001).
• F.J. McGovern et al., "Radiofrequency Ablation of Renal Cell
Carcinoma via Image Guided Needle Electrodes," J. Urol. 161
(2), 599–600 (1999).

35. Thank you