Topics included:- Introduction; General structure and basic components of TDDS; Types of TDDS; Formulation; Evaluation and it's types; Market share; Examples; Merits and demerits;

1. TRANSDERMAL DRUG DELIVERY
SYSTEM (TDDS)
FORMULATION & EVALUATION
SUBJECT : PHARMACEUTICS AND NANOTECHNOLOGY
BY-
S. DASH

3. INTRODUCTION
Trans means across & dermal means skin. Therefore, transdermal means across the
skin.
(TDDS) are defined as self contained, discrete dosage forms which are also known as
“patches”. These patches are applied to the intact skin, deliver the drug through the
skin at a controlled rate to the systemic circulation.
The first adhesive transdermal delivery system (TDDS) patch was approved by the
Food and Drug Administration in 1979 (scopolamine patch for motion sickness).
Nitroglycerine patches were approved in 1981.

4. GENERAL STRUCTURE AND BASIC
COMPONENTS OF TDDS

5. GENERAL STRUCTURE OF TDDS
 All such transdermal dosage forms have a basic structure comprising of many
layers, each having specific function.
1. Farthest from the skin, when the system is in place, is a backing layer,
preventing wetting of the system during use.
2. The second layer is a reservoir that supplies a continuous quantum of drug
for the predetermined functional life-time of the system.
3. Next to the reservoir is the rate control polymeric membrane which regulates
the rate of drug during predetermined time interval. The drug so delivered
diffuses through the skin and enters the systemic circulation.
4. Next is the adhesive layer it keeps the TDDS in contact with the skin and
final layer is the liner which protect the drug during the storage.

6. PROPERTIES OF THE DRUG USED IN TDDS
 PHYSIOCHEMICAL PROPERTIES :
1. The drug should have a molecular weight of less than approximately 1000
daltons.
2. The drug should have affinity for both lipophilic and hydrophilic phases.
3. The drug should have low melting point.
 BIOLOGICAL PROPERTIES :
1. The drug should be potent with the daily dose of the order of a few mg/day.
2. The half life of the drug should be short.
3. Drug which degrade in the GI tract or rare inactivated by hepatic first-pass
effect suitable candidates for transdermal delivery.

7. PREPARARTION
OF TDDS
TYPES
POLYMER
MEMBRANE
PERMEATION
CONTROLLED
TDDS
ADHESIVE
DIFFUSION
CONTROLLED
TDDS
MATRIX
DIFFUSION
CONTROLLED
TDDS
MICRORESERVOIR
CONTROLLED
TDDS

8. POLYMER MEMBRANE PERMEATION
CONTROLLED TDDS
In this system, the drug reservoir is embedded between an impervious
backing layer and a rate controlling membrane. The drug releases only
through the rate controlling membrane, which can be micro porous or
non-porous. In the drug reservoir compartment, the drug can be in the
form of a solution, suspension, or gel or dispersed in solid polymer
matrix.
Example : Scopolamine

9. ADHESIVE DIFFUSION CONTROLLED TDDS
The drug reservoir is formed by dispersing the drug in an adhesive polymer and
then spreading the medicated polymer adhesive by melting the adhesive (in case
of hot-melt adhesives) onto an impervious backing layer. The drug reservoir
layer is then covered by a non-medicated rate controlling adhesive polymer of
constant thickness to produce an adhesive diffusion controlling drug delivery
system.
Example : Isosorbide dinitrate for Angina Pectoris

10. MATRIX DIFFUSION CONTROLLED TDDS
The drug is dispersed homogenously in a hydrophilic or lipophilic polymer
matrix. The drug containing polymer disk then is fixed onto an occlusive
base plate in a compartment fabricated from a drug-impermeable backing
layer. Instead of applying the adhesive on the face of the drug reservoir, it is
spread along the circumference to form a strip of adhesive rim.
Example : Nitro Dur (Nitroglycerin)

11. MICRORESERVOIR CONTROLLED TDDS
This drug delivery system is a combination of reservoir and matrix-
dispersion systems. The drug reservoir is formed by first suspending the drug
in an aqueous solution of water-soluble polymer and then dispersing the
solution homogenously in a lipophilic polymer to form thousands of
unreachable, microscopic spheres of drug reservoirs.
Example : Nitro Disc

12. FORMULATION

13. EVALUATION

14. PHYSIOCHEMICAL EVALUATION
 INTERACTION STUDIES
These are done by thermal studies, FTIR, UV and chromatographic techniques by comparing their
physicochemical properties like assay, melting point, wave numbers, absorption maxima.
 THICKNESS OF THE PATCH
The thickness of the drug prepared patch is measured by using a digital micrometre at different point of
patch and determines the average thickness and standard deviation for the same to ensure the thickness of
the prepared patch.
 WEIGHT UNIFORMITY
The prepared patches are to be dried at 60ºC for 4 hours before testing. A specified area of patch is to be
cut in different parts of the patch and weigh in digital balance. The average weight and standard deviation
values are to be calculated from the individual weights.

15.  WATER VAPOUR PERMEABILITY (WVP) EVALUATION
WVP=W/A
Where W is the amount of vapor permeated through the patch expressed in gm/24 hours and A is the surface
area of the exposure samples expressed in metres.
 DRUG CONTENT
A specified area of path is to be dissolved in a suitable solvent in specific volume. Then the solution is to be
filtered through a filter medium and analyse the drug with suitable methods like UV or HPLC technique.
 PROBE TACK TEST
In this test, the tip of a clean probe with a defined surface roughness is brought into contact with adhesive, and
when a bond is formed between probe and adhesive. The subsequent removal of the probe mechanically
breaks it. The force required to pull the probe away from the adhesive at fixed rate is recorded as tack and it is
expressed in grams.
Few other physiochemical evaluation include- folding endurance studies, percentage moisture
content, content uniformity test, percentage elongation test, stability studies and many more.

16. IN VITRO EVALUATION
a. In vitro drug release studies :-
• The paddle over disc method can be employed for assessment of the release of the drug from
the prepared patches.
• Dry films of known thickness is to be cut into definite shape, weighed and fixed over a glass
plate with an adhesive.
• The glass plate was then placed in a 500ml of dissolution medium or phosphate buffer (pH-
7.4), and the apparatus was equilibrated to 32ºC.
• The paddle was then set at a distance of 2.5cm from the glass plate and operated at a speed of
50 rpm.
• Samples (5 ml aliquots) can be withdrawn at appropriate time intervals up to 24 hours and
analysed by UV spectrophotometer or HPLC.

17. a. In vitro skin permeation studies
• Full thickness abdominal skin of male Wistar rats weighing 200-250 grams. Hair from the
abdominal region is carefully removed by using an electric clipper.
• The dermal side of the skin was thoroughly cleaned with distilled water to remove any adhering
tissues or blood vessels.
• Equilibrate for an hour in dissolution medium or phosphate buffer pH-7.4 before starting the
experiment and was placed on a magnetic stirrer with a small magnetic needle for uniform
diffusion of diffusant.
• The temperature of the cell was maintained at 32ºC using a thermostatically controlled heater.
• The isolated rat skin piece is to be mounted between the compartments of the diffusion cell, with
the epidermis facing upward into the donor compartment.
• Sample volume of definite volume is to be removed from the receptor compartment at regular
intervals, and an equal volume of fresh medium is to be replaced. Samples are to be filtered
through filtering medium and can be analysed spectrophotometrically or HPLC.
• Flux can be determined directly as the slope of the curve between the steady-state values of the
amount of drug permeated vs time in hours.

19.  Animal Model
 Most common animal species used for evaluating TDDS are mouse, hairless rat, hairless dog,
hairless rhesus etc.
 Rhesus monkey is one of the most reliable models for in vivo evaluation of TDDS in animals.
 Human volunteers
 The final stage of the development of a transdermal device involves collection of pharmacokinetic
and pharmacodynamic data following application of the patch to human volunteers. It is divided
into 4 phases :-
 PHASE-1 Conducted to determine safety in volunteers.
 PHASE-2 Conducted to determine the effectiveness in patients.
 PHASE-3 Conducted to check the safety and efficiency of the drug in large number of patient
population.
 PHASE-4 Conducted to detect the adverse drug reactions on the patients’ body.

20. MARKET SHARE

21. EXAMPLES

22. MERITS :
• Avoidance of first-pass effect.
• Long duration of action.
• Ease of termination of drug action, if necessary.
• No interference with gastric and intestinal fluids.
• Suitable for administration of drugs having-
 Very short half-life, e.g. nitroglycerine.
 Narrow therapeutic window.
 Poor oral availability.

23. DEMERITS :
• Poor diffusion of large molecules.
• Skin irritation.
• Requires drug load.
• Unsuitable if drug dose is large.
• Absorption varies with different sites of skin.

24. REFERENCES :
• Chandrasekaran, S. K., & Shaw, J. E. (1977). Design of transdermal therapeutic
systems. In Contemporary topics in polymer science (pp. 291-308). Springer, Boston,
MA.
• Shaw, J. E. (1980). Drug delivery systems. In Annual Reports in Medicinal
Chemistry (Vol. 15, pp. 302-315). Academic Press.
• Keleb, E., Sharma, R. K., Mosa, E. B., & Aljahwi, A. A. Z. (2010). Transdermal drug
delivery system-design and evaluation. International Journal of Advances in
Pharmaceutical Sciences, 1(3).
• Patel, D., Chaudhary, S. A., Parmar, B., & Bhura, N. (2012). Transdermal drug
delivery system: a review. The pharma innovation, 1(4).

25. THANK YOU