Transdermal Drug Delivery System - Introduction, Iontophoresis, Advantages, Disadvantages

1. TRANSDERMAL DRUG
DELIVERY SYSTEM
Name: Akshit Chourasia.
Branch/ Year: M – Pharm Pharmaceutics (1st Year).
Roll No: 504.
Guided By: Dr. Sanjeevani Deshkar.

2. Contents:
 Introduction.
 Iontophoresis
 Advantages of Transdermal Drug Delivery System.
 Disadvantages Transdermal Drug Delivery System.
 Barriers for drug permeation.
 Penetration Enhancers.
2

3. INTRODUCTION
Transdermal Drug Delivery System
3

4. Transdermal Drug Delivery System (TDDS)
 Transdermal Drug Delivery involves drug diffusion through distinct layers of
the skin into systemic or blood circulation to provoke therapeutic effect.
 Transdermal Drug Delivery has made an important contribution to medical
practice but has yet to fully achieve its potential as an alternative to oral
delivery and hypodermic injection.
 First – generation transdermal delivery systems have continued their steady
increase in clinical use for delivery of small, lipophilic, low dose drugs.
4

5. Fig: Transdermal Drug Delivery System
5

6. Introduction (Contd…)
 Second Generation delivery systems using chemical enhancers, non –
cavitational ultra – sound and iontophoresis have also resulted in clinical
products; the ability of iontophoresis to control delivery rates in real time
provides added functionality.
 Third – generation delivery systems target their effects to skin barrier layer of
stratum corneum using micro needles, thermal ablation, microdermabrasion,
electroporation and cavitational ultrasound.
6

7. FIG: NO OF TRANSDERMAL
DRUGS APPROVED BY FDA
SINCE 1ST APPROVAL IN
1979

8. Transdermal Drugs Approved by FDA
Approved Year Drug Indication Product Name Marketing Company
1979 Scopolamine Motion Sickness Transderm – Scop. Novartis Consumer
Health (Parsippany, NJ)
1981 Nitroglycerin Angina Pectoris Transderm – Nitro. Novartis (East
Hannover, NJ)
1984 Clonidine Hypertension Catapres – TTS. Boehringer Ingelheim
(Ridgefield, CT)
1986 Estradiol Menopausal Symptoms. Estraderm. Novartis (East
Hannover, NJ)
1990 Fentanyl Chronic Pain Duragesic Janssen
Pharmaceuticals
(Titusville, NJ)
1991 Nicotine Smoking Cessation Nicoderm, Hibitrol,
ProStep.
GlaxoSmithKline,
Novartis, Consumer
Health, Elan.
1993 Testosterone Testosterone deficiency Testoderm Alza, Mountain View
8

9. 9

10. IONTOPHORESIS

11. Iontophoresis
 Iontophoresis is a medical procedure that uses an electrical current to help
deliver medication through the skin.
 The procedure involves passing a weak electrical current through the skin while
the affected area is submerged in water.
 It has been studied for moto increase transdermal delivery for more than a
century by typically applying a continuous low – voltage current.
11

12. Iontophoresis (Contd…)
 Charged drugs are moved via electrophoresis, while weekly charged and
uncharged compounds can be moved by electroosmotic flow of water generated
by the preferential movement of mobile cations instead of fixed anions in the
Stratum Corneum.
 The strongest asset of Iontophoresis is that the rate of drug delivery scales with
the electrical current, which can be readily controlled by a microprocessor or, in
some cases the patient.
12

13. Iontophoresis and Physical Therapy
 Iontophoresis is a passive treatment meaning it does not require any
participation on the part of the patient.
 Most successful physical therapy programs require you to be actively involved
in your care.
 Active therapeutic exercises are often the most important component of your
rehabilitation to improve strength and to address maladaptive and efficient
movement patterns
13

14. Indications of Iontophoresis
 Iontophoresis is a method of transdermal drug delivery wherein a
clinician uses an electric current to promote localized, superficial
permeation of a therapeutic agent through the skin.
 Among the earliest applications of electrical current for medical
therapy was by Pivati in 1740 to treat arthritis.
 More notable advances were made during the 1800s by pioneering
scientists such as Benjamin Ward Richardson, William James
Morton, and Frtiz Franken Hauser - the latter of whom coined the
phrase “iontophoresis” in favor of “cataphoresis” which had been
used more commonly prior to the 20th century.
14

15. Indications of Iontophoresis (Contd…)
 Nomenclature notwithstanding, the indications for iontophoresis are numerous
and may involve local, regional, or systemic delivery.
 Localized delivery of therapeutic agents includes local anesthetics (e.g.,
lidocaine) and fentanyl for analgesia, retinoids, and corticosteroids to treat
scarring from acne, and antiperspirants for palmar and plantar hyperhidrosis.
 Regional applications of iontophoresis include the delivery of anti-
inflammatory agents into subcutaneous tissue and joint spaces to relieve
tendonitis, arthritis, or transient muscle soreness.
 Lastly and more rarely, systemic delivery of drugs via transdermal
iontophoresis include fentanyl for analgesia, antimigraine agents (e.g., triptan
drugs) for headache, nicotine for smoking cessation, reversible cholinesterase
inhibitors such as rivastigmine for Alzheimer disease, and even proteins or
peptides such as insulin. 15

16. Benefits of Iontophoresis
16
• Decrease Inflammation.
• Decrease Pain.
• Decrease Muscle Spasm.
• Decrease swelling and Edema.
• Reduce Calcium Deposits in the
body.
• Manage Scar tissue.

17. Advantages of Transdermal Drug Delivery System
17

18. Disadvantages of Transdermal Drug Delivery System
18

19. Barriers for Drug Penetration
19

20. Skin Barrier
 The skin is a complex organ that provides a protective barrier against the
environment.
 This barrier is composed of several layers, including the stratum corneum, the
dermis, and the epidermis.
 The stratum corneum is the outermost layer of the skin and is composed of
dead cells packed tightly together.
 This layer is the primary barrier to drug penetration.
 Other factors that can affect TDD include skin age, skin condition, and
environmental factors such as temperature and humidity.
20

21. Limited Permeability
 Limited permeability is one of the primary barriers to transdermal drug delivery
(TDD).
 The skin, the outermost layer of our bodies, acts as a formidable barrier against
the penetration of foreign substances, including drugs.
 This protective barrier, composed of the stratum corneum, dermis, and
epidermis, effectively restricts the movement of molecules into and out of the
body.
 The stratum corneum, the outermost layer of the skin, is the main culprit behind
limited permeability.
 It's a densely packed layer of dead skin cells held together by ceramides, fatty
acids, and cholesterol. This tight arrangement forms a brick-and-mortar-like
structure that impedes the passage of most drugs.
21

22. Factors contributing to limited Permeability
Factors to limited
Permeability
Molecular Size
Larger molecules, such as
proteins and peptides,
have difficulty squeezing
through the tight junctions
between skin cells.
Drug Polarity
Highly polar drugs, those
with a strong affinity for
water, tend to get stuck
within the stratum
corneum and struggle to
penetrate deeper layers.
Drug Solubility
Drugs that are poorly
soluble in both water and
lipids have limited ability
to diffuse across the skin
barrier.
Skin Thickness
The thickness of the
stratum corneum varies
across different body
parts.
Thinner skin, like that on
the face and neck, allows
for easier drug penetration
compared to thicker skin
on the back and palms.
22

23. Strategies to overcome barriers of TDDS
There are several strategies that can be used to overcome the barriers to TDD.
These include:
• Formulating the drug in a way that enhances its penetration, such as using
prodrugs or chemical enhancers.
• Using physical methods to disrupt the skin barrier, such as microneedles or
sonophoresis.
• Applying the drug to a site where the skin is thinner and more permeable.
23

24. PENETRATION ENHANCERS
24

25. Penetration Enhancement
 Skin Penetration enhancement
techniques have been developed to
improve bioavailability and increase
the range of drugs for which topical
and transdermal delivery acts.
 Penetration enhancers penetrates
through skin to decrease the barrier
resistance.
 Alternatively, physical mechanism
such as iontophoresis &
phonophoresis can be used for certain
cases of drugs.
25

26. Action of Penetration Enhancers
26

27. Desirable Properties of Penetration Enhancers
 Non – toxic, non – irritating and non – allergic.
 Rapid working.
 Predictable and reproducible duration of action.
 No pharmacological activity within the body.
 When removed from the skin, barrier properties should return both rapidly and
fully.
 Compatible with both excipients and drugs.
 Cosmetically acceptable.
27

28. Classification of Penetration Enhancers
Penetration
Enhancers
Physical
Enhancers
Chemical
Enhancers
Drug Vehicle
Based
Natural
Penetration
Miscellaneous
Biochemical
Approach
28

29. Physical Enhancers
29
• Physical penetration enhancers use physical methods to disrupt the skin's
barrier properties and enhance drug penetration.
• These enhancers can be further subdivided into several classes:
a) Occlusion: Occlusive agents form a physical barrier on the skin, preventing
water evaporation and increasing skin hydration. This can enhance drug
penetration by increasing the permeability of the stratum corneum.
Examples include petrolatum, mineral oil, and lanolin.
b) Iontophoresis: Iontophoresis uses an electric current to drive charged drug
molecules across the skin. This method is particularly useful for delivering
drugs with poor permeability through the skin.
c) Sonophoresis: Sonophoresis uses ultrasound waves to create transient pores
in the skin, allowing for enhanced drug penetration.
d) Microneedles: Microneedles are tiny needles that can be inserted into the
skin to create microchannels for drug delivery.

30. Chemical Enhancers
 Chemical Enhancers or penetration enhancers or absorption promotes are the
agents that interact with skin constituents to promote the drug flux.
 Many agent have studied and evaluated for enhancement properties.
 Yet their inclusion in skin formulation is titrated due to unknown mechanism
and toxicity.
 Example: Sulfoxide, Azones, Surface Active Agents, Amines & Amides, Fatty
Acids, etc.
30

31. Biochemical Penetration Enhancers
 Biochemical penetration enhancers interact with the skin's biochemical
processes to facilitate drug penetration.
 These enhancers can be further subdivided into several classes:
a) Enzyme inhibitors: These enhancers inhibit enzymes that break down the
drug or reduce its permeability through the skin. Examples include protease
inhibitors and lipase inhibitors.
b) Lipid-modifying agents: These enhancers modify the composition of the
skin's lipids to make it more permeable to the drug. Examples include
ceramides and sphingomyelin.
c) Vasodilators: These enhancers increase blood flow to the skin, which can
enhance drug penetration by increasing the delivery of the drug to the target
site. Examples include niacin and histamine.
31

32. Uses of Penetration Enhancers
1. To increase the delivery of ionisable drugs.
2. To deliver the impermeable drugs.
3. To maintain level of drug into the blood stream.
4. To improve the efficacy of less potent drugs with higher dose.
5. To deliver the drugs having higher molecular weight.
6. To decrease the lag time of transdermal drug delivery system.
32

33. Merits of Penetration Enhancers
1. Enhanced drug absorption and penetration.
2. Non-invasive delivery.
3. Targeted drug delivery.
4. Improved stability and solubility.
5. Versatility.
6. Potential for synergistic effects.
33

34. Demerits of Penetration Enhancers
1. Skin irritation.
2. Allergic reactions.
3. Systemic exposure.
4. Instability of formulations.
5. Limited selectivity.
6. Potential for toxicity.
7. Regulatory challenges.
34

35. References
35
1. Chein. Y. B. Novel Drug Delivery Systems, 2nd Edition, Page No – 338 to
380.
2. Dmitriy Berillo, Zharylkasyn Zharkinbekov, Yevgeniy Kim, Kamila
Raziyeva, Kamila Temirkhanova and Arman Saparov – Review Article on
Stimuli Responsive Polymers for Transdermal, Transmucosal & Ocular
Drug Delivery System, 2021.
3. https://www.sciencedirect.com/topics/medicine-and-dentistry/transdermal-
drug-
administration#:~:text=Transdermal%20drug%20delivery%20involves%20
drug,circulation%20to%20provoke%20therapeutic%20effect/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700785/
5. https://solutionpharmacy.in/transdermal-drug-delivery-system/
6. https://www.fvpt.com/iontophoresis

36. THANK YOU
36