This document provides an overview of transdermal drug delivery systems (TDDS). It discusses the definition of TDDS, advantages like avoiding first-pass metabolism, and disadvantages like molecular size restrictions. The basic components of TDDS are described as the polymer matrix, drug, permeation enhancers, and other excipients. Methods for evaluating TDDS are also summarized, including physiochemical evaluation of properties like thickness and drug content, in vitro evaluation through drug release and permeation studies, and in vivo animal and human studies.

1. TRANSDERMAL DRUG DELIVERY SYSTEM
PRINCE THAKUR
M . Pharmacy
1st Year

2. CONTENTS
Introduction
* Definition
* Advantages
* Disadvantages
Basic components of Transdermal Drug Delivery System
1. Polymer Matrix
2. Drug/API
3. Permeation Enhancers
4.Other Excipients
Evaluation of Transdermal Drug Delivery System
A: Physiochemical Evaluation.
B: In-Vitro Evaluation.
C: In-Vivo Evaluation.

3. Definition:
 Transdermal Drug Delivery System, also known as “patches” are dosage forms designed to
deliver a therapeutically effective amount of drug across a patient’s skin.
 The drug initially penetrates through the Stratum corneum and then passes through the deeper
Epidermis and Dermis without drug accumulation in the Dermal layer, it becomes available for
systemic absorption via the dermal microcirculation.

4. Advantages:
1. Avoids first pass metabolism.
2. Convenient.
3. Improved patient compliance.
4. Self administration.
5. No interaction with gastric contents.
Disadvantages:
# Molecular size restriction(<500 Dalton)
# High cost.
# Local irritation / un-comfortibility.
# Low levels in blood/plasma.
# No rapid drug release.
# Variation in barrier function (Age , Site).

5. Basic Components of Transdermal drug delivery system
It includes:
(1). Polymer Matrix.
(2). Drug/API.
(3).Permeation Enhancers.
• Solvents.
• Surfactants.
(4). Other Excipients.
• Adhesives.
• Backing Membrane.

6. {A}: Polymer Matrix:
Polymer control the release of the drug from the device.
A. Molecular weight , glass transition temperature and chemical functionality of
the polymer should be such that the specific drug diffuses properly and gets
released through it.
B. The polymer should be stable , non-reactive with the drug , easily
manufactured and fabricated into the desired product; and inexpensive.
C. The polymer and its degradation products must be non toxic or non-
antagonistic to the host.
D. The mechanical properties of polymer should not be deteriorate excessively
when large amounts of active agents are incorporated into it.
Examples: 1. Natural Polymers:-Cellulose derivatives , Zein , Gelatin , Shellac ,
Waxes, Proteins, Gums, Natural Rubber.

7. 2. Synthetic Elastomers:- Has extremely weak inter-molecular forces.
Examples: Polybutadiene, Hydrin rubber ,Polysiloxane , Silicone rubber,
Nitrile , Styrene butadiene,Rubber , Neoprene etc.
3. Synthetic polymers:- Polyvinyl alcohol, Polyvinyl chloride, Polyethylene,
Polypropylene, Polyurea.
4. Semi-Synthetic Polymer:- HPMC ,HPC ,EC.
{B}: Drug:
For successfully developing a transdermal drug delivery system, the drug
Should be chosen with great care. DOSE 20mg/day.
Some following desirable properties of a drug for transdermal delivery:-
Physicochemical Properties:-
1. Drug should have molecular weight less than approx. 1000 Daltons.
2. Drug should have affinity for both lipophilic and hydrophilic phases.
3. Extreme partitioning characteristics are not conductive to successful drug
delivery via the skin.
4. Drug should have a low melting point.

8. Biological Properties:-
• The drug should be potent with a daily dose of a few mg/day.
• The half life (t1/2) of the drug should be short.
• The drug must not induce a cutaneous irritant or allergic response.
• Drugs which degrade in the GI Tract or are inactivated by hepatic first-pass
effect
are suitable candidates for transdermal delivery.
• Tolerance to the drug must not develop under the near zero-order release profile
of transdermal delivery.
• Drugs which have to be administered for a long period of time or which cause
adverse effects to non-target tissues can also be formulated for transdermal
delivery.

9. {C}: Permeation Enhancers:
These are compounds which promote skin
permeability by altering the skin as a barrier to the flux of a desired penetrant.
The flux, J of drugs across the skin can be written as:
Where D is the diffusion coefficient and is a function of the size, shape and
flexibility of the diffusing molecule as well as membrane resistance;
C is the concentration of the diffusing species;
X is the spatial co-ordinate.
dc/dx is the concentration gradient of the diffusing species.

10. (1): Solvents: These compounds increase penetration possibly by swelling the polar
pathway and / or by fluidizing lipids.
Examples; Water alcohols-methanol and ethanol, alkyl methyl sulfoxides- dimethyl
sulfoxide, dimethyl acetamide .
(2): Surfactants: These compounds are proposed especially of hydrophilic drugs.
The ability of a surfactant to alter penetration is a function of the polar head group
and the hydrocarbon chain length.
 Anionic surfactants can penetrate and interact strongly with the skin. Once these
surfactants have penetrated the skin , they can induce large alterations.
 Cationic surfactants are reportedly more irritant than the anionic surfactants and
they have not been widely studied as skin permeate on enhancers.

11. Examples:
• Anionic Surfactants:- Dioctyl sulphosuccinate, Sodium Lauryl Sulphate, Deco-decylmethyl
sulphoxide.
• Non-ionic Surfactants:- Pluronic F127, Pluronic F68, etc.
• Bile salts:- Sodium taurocholate , Sodium deoxycholate, Sodium tauroglycocholate.
{D}: Other Excipients:-
* Adhesives: For fastening of all transdermal devices to the skin by using pressure sensitive
adhesive.
Ideal Characteristics:
a. It should be adhere to the skin aggressively during the dosing interval without its position being
distributed by activities such as Bathing, Exercise etc.
b. It should be easily removed.
c. It should not leave an un-washable residue on the skin.
d. It should have excellent (intimate) contact with the skin at macroscopic and microscopic level.
e. It should not irritate or sensitize the skin or cause an imbalance in the normal skin flora during
its contact time with the skin.

12. * Backing membrane:
 It is flexible.
 It provide good bond to the drug reservoir.
 It prevent drug from leaving the dosage form .
 The Function depends on the Design of the specific system .
 The size of the active component and the need to have a Rate-Limiting Factor in order to satisfy
the Release and Absorption characteristics of the system.
 Having Good Diffusion properties.
Examples: Ethylene vinyl acetate, Silicone rubber, Polyurethrane.

13. Roles of Rate Controlling Membrane:
To Limit the Flow of the semi-solid content from the Liquid Reservoir , and / or to act as a Rate-Limiting
Membrane for Both Liquid reservoir and matrix systems.
Types of Membrane:
 Ethylene Vinyl acetate membranes.
 Microporous polyethylene membranes.

14. Evaluation of Transdermal Drug Delivery System
METHODS
Physiochemical In-Vitro Evaluation In-Vivo Evaluation
evaluation
 Interaction Studies. # In-Vitro drug release * Animal Model.
 Thickness of the patch. Studies. * Human Model.
 Weight uniformity.
 Percentage of moisture content. # In-Vitro skin permeation
 Water vapour permeability studies.
(WVP) Evaluation.
 Drug Content.
 Content uniformity test.
 Probe Tack test.
 Percentage elongation break
Test.
 Stability Test.,

15. (A). Physiochemical Studies:-
a: Interaction Studies:
 These studies are taken out by Thermal Analysis, FTIR,UV and Chromatographic techniques by
comparing their physiochemical properties like assay, melting point, wave numbers, absorption
maxima.
b: Thickness of Patch:
 Measured by using a digital micrometer at different point of patch and determines the average
thickness and standard deviation for the same to ensure the thickness of the prepared patch.
c: Weight Uniformity:
 The prepared patches are dried at 60˚C for 4 Hours before testing.
 A specified area of patch is to be cut in different parts of the patch and weight in digital balance.
 The average weight and standard deviation values are to calculated from the individual weights.

16. d: Water vapour permeability (WVP) Evaluation:
Water vapour permeability can be determined by a natural air circulation oven. The WVP can be
determined by the following formula :
WVP= W/A
W= is the amount of vapour permeated through the patch expressed in gm/ 24 hours.
A= is the surface area of the exposure samples expressed in m.
e: Drug content:
A specified area of patch is to be dissolved in a suitable solvent in specific volume.
Then the solution is to be filtered through a filter medium and analyses the drug contain with
the suitable method (UV or HPLC technique).

17. f: Content Uniformity Test:
10 patches
Content is determined for individual patches
If 9 out of 10 patches have content between 85 -115%
And one has contentment not less than 75-125%
Patch pass this test

18. But if 3 patches have content about 75-125%
then additional 20 patches are tested for drug content
If these 20 patches have range from 85-115%
then the transdermal patch PASS the TEST

19. g: Moisture Content: the prepared films are weighed individually and kept in a dessiccators
containg Calcium Chloride at room temperature for 24 hours.
The films are weighed again after a specified interval
Until they show a constant weight.
The percent moisture content is calculated by:
% Moisture content= Initial Weight – Final weight * 100

20. h: Stability Studies:
 Stability studies are to be conducted according to the ICH storing the TDDS sample at 40 + 0.5
degree Celsius and 75 - 5% RH for 6 months.
 The samples were withdrawn at 0,30,60,90 and 180 days and analyze suitability for the
Drug Content.
(B): In-Vitro Evaluation of TDDS:
(1) In-Vitro drug release studies:
The paddle over disc method(USP apparatus V) can be employed for assessment
of the release of the drug from the prepared patches.
Drug films of known thickness is to be cut into definite shape, weighed, and fixed over a glasss
plate with an adhesive.

21. The glass plate was then placed in a 500 ml of the dissolution medium or phosphate buffer (pH 7.4), and the
apparatus was equilibrated to 32 + 0.5 degree Celsius.
The paddle was then set a distance of 2.5 cm from the glass plate and operated at a speed of 50 rpm.
Samples (5ml) can be withdrawn at appropriate time intervals up to 24 hours and analysed by UV-
Spectrophotometer or HPLC.
The experiment is to be performed in triplicate and the mean value can be Calculated.

22. (2) In-Vitro skin permeation studies:
 In these studies, excised skin is mounted on skin permeation cells.
 Skin of hairless mouse is used rather than human cadaver skin.
 An in-vitro permeation study can be carried out by using:
Examples: Franz Diffusion Cell.
(C): In-Vivo Evaluation:
# Animal Model: Animal Studies on small scale .The most common dt species for evaluating
TDDS are mouse, hairless dog, hairless rhesus monkey.
Rhesus Monkey is one of the most reliable models or in-vitro evaluation of TDDS in evaluation.
# Human Models: Final stage of the development of transdermal device involves collection
of Pharmacokinetic and Pharmacodynamic date collected.

23. Clinical Trials: have bee conducted to asses the efficacy, risk involved, side effects, patient
compliance etc.
Phase-1: Determine safety in volunteers.
Phase-2: Determine short term safety and mainly effectiveness in patients.
Phase-3: Safety and effectiveness in large number of patient population.
Phase-4: Post Marketing Surveillance are done for marketed patches to detect adverse drug
reactions.
# Skin Irritation Study: or sensitization testing performed on healthy rabbits.
 Patch is remain contact with skin for 24 hours.
 Selection of patch on the basis of the severity of skin injury.

24. THANK YOU