Transdermal drug delivery system (TDDS)

1. TRANSDERMAL DRUG
DELIVERY SYSTEM
PRESENTER:
PHARM MUHAMMAD AMINU
IBRAHIM
SUPERVISED BY:
PHARM LUKMAN BASHIR
1

2. OUTLINE
2
 Introduction
 Drug delivery system
 Transdermal Drug delivery system
 Anatomy and Physiology of skin
 Route of drug Permeation of Skin
 Ideal properties of drugs for TDDS
 Release kinetic
 Component/ patches used in TDDS
 Types of patches
 Recent advancement in TDDS
 Marketed product of TDDS
 Conclusion
 References

3. Introduction
3
 The concept of delivering drugs through the skin was first
introduced in the early 1950s (Sinko 2011).
 The first commercial product was made available in the United
States in early 1980s (Sinko 2011).
 These first-generation, passive, transdermal patches were designed
to control nausea, vomiting, angina, however, failed to succeed in
the market.
 The introduction of nicotine patches for smoking cessation gave the
necessary impetus to this technology during the initial years.
 Today transdermal patches are widely used to deliver hormones
and pain management medications.
 The market for transdermal devices has been estimated at U.S. $2
billion; This figure represents 10% of the overall U.S. $28 billion
drug delivery market (Barry 2001).

4. Drug delivery system
4
Refers to formulations, technologies, and
systems for transporting a pharmaceutical
compound to a specific site in the body at
certain rate as needed to safely achieve its
desired therapeutic effect.
(Sinko 2011)

5. TRANSDERMAL DRUG DELIVERY SYSTEM
(TDDS)
5
Defined as the topically administered
medications in self-contained, discrete dosage
forms of patches which when applied to the
skin deliver the drug, through the skin portal to
systemic circulation at a predetermined and
controlled rate over a prolonged period of time,
in order to increase the therapeutic efficacy
and reduced side effect of drug.
(Bala et al., 2014)

6. Advantages
6
(Bala et al., 2014)

7. Disadvantages
7
(Bala et al., 2014)

8. COMPARISON BETWEEN IV,ORAL AND
TDDS
8
S/N ADVANTAGES IV ORAL TDDS
1 Avoid hepatic first pass effect YES NO YES
2 Constant drug levels YES NO YES
3 Self administration NO YES YES
4 Termination of therapy NO YES YES

9. Anatomy and physiology of skin
9
 Skin is multi-layered organ composed of many
histological layers.
 It covers an area of about 2m2 and 4.5-5 kg i.e. about
16% of total body weight in adults.
 Thickness is in range of 0.5mm (on eyelids) to 4.0mm
(on heels).
 The main function of the skin is to provide a protective
barrier between the body and the external
environment against microorganisms, UV radiation,
chemicals, allergens and the loss of water.
(Ahlam et al., 2015)

10. Layers of skin
10
 Epidermis: the outermost layer, which
contains the stratum corneum
 Dermis: the middle layer
 Hypodermis: inner most layer
(Ahlam et al., 2015)

11. Routes of drug permeation of
skin11
Transcorneal penetration
 Intracellular penetration (between the cells): Drug
molecule passes through the cells of the stratum
corneum. It is generally seen in case of hydrophilic
drugs.
 Intercellular penetration (across lipid rich region):
These molecules dissolve in and diffuse through the
non-aqueous lipid matrix imbibed between the protein
filaments.
(Rastogi 2012)

12. Epidermal route for drug
permeation12
(Syeda et al., 2017)

13. Routes of drug permeation of
skin13
Transappendegeal penetration
 This is also called the shunt pathway.
 In this route, the drug molecule may transverse
through the hair follicles, the sebaceous
pathway of the pilosebaceous apparatus or the
aqueous pathway of the salty sweat glands.
(Rastogi 2012)

14. Ideal properties of drugs for
TDDS14
Parameters Properties
Dose Should be low (low than 20 mg/day)
Half-life 10 or less (h)
Molecular weight <400 Dalton
Partition Coefficient Log P (octanol-water) between 1.0 and 4.0
Liophilicity High
Oral bioavailability Low
Therapeutic index Low
Melting point <200°C
pH Between 5.0 and 9.0
(Syeda et al., 2017)

15. Release kinetic
15
 Release of drug through Stratum cornium
follows fick’s law of diffusion which states
that ‘the rate of diffusion (flux) is proportional
to both the surface area and concentration
difference and is inversely proportional to the
thickness of the membrane’.

16. Release kinetic cont…
16
Where;
Where; (Cs-Cv)=concentration
gradient
P=permeability
coefficient
A=surface area
But Cs>>>Cv D=diffusion
coefficient
K=partition coefficient

17. BASIC COMPONENTS OF
TDDS17
 Polymer matrix/drug reservoir
 Membrane
 Drug
 Permeation enhancers
 Backing laminates
 Release liner
 Other excipients;
like plasticizers and solvents
(Rastogi and Yadav 2012)

18. Types of Transdermal Patch
18
 Old/first generation (Passive)
 Recent advancement (Active)

19. Old/first generation (Passive)
19
 Single-layer Drug-in-Adhesive
 Multi-layer Drug-in-Adhesive
 Reservoir
 Matrix
(Patel et al., 2012)

20. 1.Single-layer Drug-in-
Adhesive20
 In this type of patch the adhesive layer not
only serves to adhere the various layers
together, along with the entire system to the
skin, but is also responsible for the releasing
of the drug.
 The adhesive layer is surrounded by a
temporary liner and a backing.

21. 2.Multi-layer Drug-in-
Adhesive21
 The multi-layer drug-in adhesive patch is
similar to the single-layer system in that both
adhesive layers are also responsible for the
releasing of the drug.
 The multi-layer system is different however
that it adds another layer of drug-in-adhesive,
usually separated by a membrane (but not in
all cases).
 This patch also has a temporary liner-layer
and a permanent backing.

22. 3. Reservoir
22
 The drug layer is a liquid compartment
containing a drug solution or suspension
separated by the adhesive layer.
 This patch is also backed by the backing layer.
 In this type of system the rate of release is
zero order.

23. 4. Matrix
23
 The Matrix system has a drug layer of a
semisolid matrix containing a drug solution or
suspension.
 The adhesive layer in this patch surrounds the
drug layer partially overlaying it.

24. Recent advancement in TDDS
24
 Iontophoresis.
 Electroporation.
 Microneedle
 Sonophoresis
 Needle-less Injection
 Skin Abrasion
 Laser Radiation
 Thermophoresis
 Electro-Osmosis
 Microporation

25. 1.Iontophoresis
25
 It involves passing of current (few milli
amperes) to a limited area of the skin using
electrode.
 The electrode remains in contact with the
formulation to be administered.
 Pilocarpine delivery can be taken as example
to induce sweat in the diagnosis of cystic
fibrosis and Iontophoretic delivery of lidocaine
is considered to be a nice approach for rapid
onset of anesthesia.
(Ahlam et al., 2015)

26. Iontophoresis cont….
26

27. Iontophoresis cont….
27

28. 2.Electroporation
28
 Involves the application of high-voltage pulses to
induce skin perturbation.
 High voltages (≥100 V) and short treatment durations
(milliseconds) are most frequently employed.
 The increase in skin permeability is suggested to be
caused by the generation of transient pores during
electroporation.
 The technology has been successfully used to
enhance the skin permeability of molecules with
differing lipophilicity and size (i.e., small molecules,
proteins, Peptides, oligo nucleotides).
 Anticancers drugs such as bleomycin can be
administered through this method.
(Ahlam et al

29. Electroporation cont…
29

30. 3.Microneedles
30
 Drugs is deliver into the skin by invasive
manner.
 Solid micro needles have been shown to
painlessly pierce the skin to increase skin
permeability to a variety of small molecules,
nanoparticles and proteins from an extended-
release patch.
 Microneedles are needles that are 10 to 200
μm in height and 10 to 50 μm in width.
 Microneedles do not stimulate the nerves, so
the patient does not experience pain or

31. Microneedles cont…
31
 They are usually drug coated projections of
solid silicon or hollow, drug filled metal
needles.
 Microneedles have been dip coated with a
variety of compounds such as small
molecules, DNA, proteins, and virus particles.
 E.g. of drug used : riboflavin, pilocarpine.

32. Microneedles cont….
32

33. 4.Ultrasound (phonophoresis,
sonophoresis)33
 This technique was used originally in physiotherapy
and sports medicine.
 It uses an ultrasound sources to increase drug
permeation through the skin.
 The procedure was extended to transdermal drug
delivery studies.
 The ultrasonic energy (at low frequency) disturbs the
lipid packing in SC by cavitation.
 Shock waves of collapsing vaccum cavities increase
free volume space in bimolecular leaflets and thus
enhance drug penetration into the tissue.
 Drug like hydrocortisone can be used to enhanced
penetration through the skin.
(Ahlam et al., 2015)

34. Sonophoresis cont…
34

35. 5.Needle-Less Injection
35
 In this transdermal delivery system, the liquid
or solid particles are fired at supersonic
speeds through the outer layers of the skin
using a reliable energy source for delivering
the drug.
 The mechanism is basically, forcing
compressed gas (helium) via a nozzle, such
that the resultant drug particles entrained
within the jet flow that travels at sufficient
velocity for skin penetration.
(Ahlam et al., 2015)

36. Needle-Less Injection cont…
36

37. Needle-Less Injection cont…
37

38. 6.Skin Abrasion
38
 In this technique, the upper layers of the skin
is directly removed so that it easily helps in
permeation of topically applied medicaments.
 There are also some devices that are based
on this technique which are employed by
dermatologists for superficial skin resurfacing
(e.g. micro dermabrasion).
 They have use in the treatment of acne,
scars, hyper pigmentation and other skin
blemishes.

39. Skin Abrasion cont…
39

40. 7.Laser Radiation
40
 This method involves direct and controlled
exposure of a laser to the skin which results in the
ablation of the stratum corneum without
significantly damaging the underlying epidermis.
 Removal of the stratum corneum using this
method has been shown to enhance the delivery
of lipophilic and hydrophilic drugs.
 Photomechanical waves significantly increase
stratum cornea permeability to drug substance
through a possible permeabilisation mechanism
due to development of transient channels.
(Preetam Bala et al., 2014)

41. Laser Radiation cont…
41

42. 8.Thermophoresis
42
Controlled Heat Aided Drug Delivery (CHADD)
System-
 In CHADD System, the transfer of drug substance to
the blood circulation takes place by applying heat to
the skin.
 that increases the temperature and ultimately leads to
increase in microcirculation and permeability of the
blood vessel. (Bala et al., 2014)
 The skin surface temperature is usually maintained at
32°C tetracaine and fentanyl from transdermal
patches with attached heating devices was shown to
increase as a result of the elevated temperature at the
site of delivery.
 However, the effect of temperature on the delivery of
penetrates greater than 500 Daltons has not been
reported.

43. 9.Electro-Osmosis
43
 To the porous membrane which is having
some charge, a voltage difference is applied to
it, thus a bulk fluid or volume flow takes place
with no concentration gradients.
 This process is known as electro -osmosis.
(Bala et al., 2014)

44. 10.Microporation
44
 Microporation involves the use of micro needles
that are applied to the skin so that they pierce only
the stratum corneum and increase skin
permeability.
 The most effective strategy for overcoming the
skin’s barrier properties has been to focus on the
creations of micropores in the stratum corneum.
 Microchannels or micropores can be created by
external means such as microneedles, ultrasound,
electroporation, radiofrequency and laser.
 The key future successes in transdermal drug
delivery of large molecules, especially
biopharmaceuticals.

45. Microporation cont….
45

46. Marketed Products of TDDS
46
PRODUCT MANUFACTURE
R
ACTIVE
DRUG
TYPES
OF
PATCH
INDICATION
Estraderm Alza/Norvatis Estradiol Membrane Postmenstrual
syndrome
Duragesic Alza/Janssen Fentanyl Reservoir Pain relief patch
Transderm-
scop
Scopolamine Matrix Motion sickness
Deponit Schwarz-Pharma Nitroglycerin
e
Drug in
adhesive
Angina pectoris
Lidoderm Lidocaine Drug in
adhesive
Anaesthetic
Androderm Thera Tech/GSK Testosterone Reservoir Hypogonadism
in males
Habitraol Novartis Nicotine Matrix Smoking
cessation
(Brown 2006)

47. Marketed Products of TDDS
47

48. Marketed Products of active
TDDS48
Company System/Device name Status
Iomed Inc. (Salt Lake City,
UT, USA)
Phoresor FDA approved for local
dermal anesthesia
Vyteris Inc. (Fair Lawn, NJ,
USA)
Lidosite FDA approved for
localized pain treatment
Cygnus Inc. (Redwood, CA,
USA)
Glucowatch FDA approved for
glucose monitoring in
diabetics
BioPhoretic Systems
(Framingham, MA, USA)
Acyclovir Direct Phase 3 clinical trials
Aciont Inc (Salt lake City, UT,
USA)
Accuresis Under development
(Brown 2006)

49. Conclusion
49
 Many new researches are going on in the
present day to incorporate newer drugs via this
system.
 In time, it is hoped that technological
advancements in TDDS will lead to enhanced
disease prevention, diagnosis and control, with
concomitant improvement in health-related
quality of life for patients worldwide.

50. References
50
 Ahlam Zaid Alkilani, Maelíosa T.C. McCrudden and Ryan F.
Donnelly. Transdermal Drug Delivery: Innovative Pharmaceutical
Developments Based on Disruption of the Barrier Properties of the
stratum corneum. Pharmaceutics 2015, 7, 438-470;
doi:10.3390/pharmaceutics7040438.
 Baichwal MR. Polymer films as drug delivery system, advances in
drug delivery system. Bombay ,MSR foundation; 1985;136-147.
 Barry, B. W. 2001. Novel mechanisms and devices to enable
successful transdermal drug delivery. Eur. J. Pharm. Sci. 14:101–
114.
 Dipen Patel, Sunita A. Chaudhary, Bhavesh Parmar, Nikunj Bhura.
Transdermal Drug Delivery System: A Review.
www.thepharmajournal.com Vol. 1 No. 4 2012;72-75.
 Keleb E,Sharma Rk, Mosa EB,. Transdermal drug delivery system-
design and evaluation. International journal of advances in

51. References cont…
51
 Kharat Rekha Sudam and Bathe Ritesh Suresh. A Comprehensive
Review on: Transdermal drug delivery systems. International
Journal of Biomedical and Advance Research 2016; 7(4): 147-159.
 Brown Marc B, Gary P. Martin, Stuart A. Jones & Franklin K.
Akomeah (2006) Dermal and Transdermal Drug Delivery Systems:
Current and Future Prospects, Drug Delivery, 13:3, 175-187, DOI:
10.1080/10717540500455975
 Bala Preetam, Sonali Jathar, Sangeeta Kale, Kavita Pal.
Transdermal Drug Delivery System A Multifaceted Approach For
Drug Delivery. Journal of Pharmacy Research 2014,8(12),1805-
1835.
 Syeda Ayesha Fathima, Shireen Begum, Syeda Saniya fatima.
Transdermal Drug Delivery System. International Journal of
Pharmaceutical and Clinical Research 2017; 9(1): 35-43.

52. References cont…
52
 Vyas SP, Khar RK. Targeted and controlled drug
delivery novel carrier system. 1st ed. CBS publishers
and distributors New Delhi; 2002;411-447.
 Vaibhav Rastogi, Pragya Yadav. Transdermal drug
delivery system: An overview. Asian Journal of
Pharmaceutics - July-September 2012;165-166.
 Wilson Ellen Jett, 2011 Three Generations: The Past,
Present, and Future of Transdermal Drug Delivery
Systems.
 Shingade, G.M., Aamer, Q., Sabale, P. M.,
Grampurohit, N.D., Gadhave, M.V.,2012. Review on:
recent trend on transdermal drug delivery system,
Journal of Drug Delivery & Therapeutics 2 (1), 66-75.

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