1.

Definition: Transdermal drug delivery system can deliver the drugs through the skin portal to
systemic circulation at a predetermined rate and maintain clinically the effective concentrations
over a prolonged period of time. T.B.EKNATH 2 BABU (T.B.E.K.B) Over the last two decades
more than 35 Transdermal patch products have been approved in US. Transdermal drug
delivery is hardly an old technology, since 1800s and the technology is no longer just adhesive
patches. Due to recent advances in technology and the ability to apply the drug to the site of
action without rupturing the skin membrane, transdermal route is becoming a widely accepted
route of drug administration. IInnttrroodduuccttiioonn
2.

Reduced inter and intra patient variability. T.B.EKNATH 3 BABU (T.B.E.K.B) Allow
administration of drugs with narrow therapeutic window because drug levels are maintained
within the therapeutic window for prolonged periods of time. Allows effective use of drugs with
short biological half-life. Avoidance of significant presystemic metabolism (degradation in GIT
or by the liver) and therefore need lower doses. No GI distress and the factors like Gastric
emptying, intestinal motility, transit time, donot effect this route as in oral route. Avoids
chemically hostile GI environment (drug degradation in acidic and basic environments is
prevented). Potential advantages of TDDS

3.

Provides suitability of self medication. T.B.EKNATH 4 BABU (T.B.E.K.B) Drug input can be
promptly interrupted simply by removal of the patch when toxicity occurs. Avoids the risk and
inconveniences of parenteral therapy (Painless method of drug administration). Can provide
adequate absorption of certain drugs. Provides controlled plasma levels of very potent drugs.
Reduction of dosing frequency and enhancement of patient compliance. Enhance
therapeutic efficacy, reduced fluctuations (rapid blood level spikes-low and high) due to
optimization of blood concentration time profile.

4.

The molecular size of the drug should be reasonable that it should be absorbed percutaneously.
T.B.EKNATH 5 BABU (T.B.E.K.B) Adequate solubility of the drug in both lipophilic and aqueous
environments, to reach dermal microcirculation and gain access to the systemic circulation.
Transdermal administration is not a means to achieve rapid bolus type drug input, rather it is
usually designed to offer slow, sustained drug delivery. Drugs that require high blood levels
cannot be administered limited only to potent molecules, those requiring a daily dose of 10mg
or less. Disadvantages of TDDS

5.

May not be economical. T.B.EKNATH 6 BABU (T.B.E.K.B) Uncomfortable to wear. Adhesive

may not adhere well to all types of skin. Skin irritation or dermatitis due to excipients and
enhancers of drug delivery system used for increasing percutaneous absorption is another major
limitation. Difficulty of permeation of the drug through human skin barrier function of the skin.
Tolerance inducing compounds are not an intelligent choice for this mode of administration
unless an appropriate wash out period is programmed in between the dosing regimen.

6. Cross-section of human skin T.B.EKNATH 7 BABU (T.B.E.K.B)

7. Stratum Corneum (topmost 15 m layer) is the main barrier T.B.EKNATH 8 BABU (T.B.E.K.B)
8. Pathways of drug penetration 1.Through stratum corneum 2.Transfollicular 3.9 T.B.EKNATH
BABTU h(Tro.Bu.Eg.hK. Bsw) eat gland
9. Mechanisms of drug permeation Hydrophilic drugs permeates by Intercellular pathway and
Lipophilic drugs permeates by Intracellular (Transcellular) mechanism. T.B.EKNATH 10 BABU
(T.B.E.K.B)
10. C is the drug concentration gradient across the skin T.B.EKNATH 11 BABU (T.B.E.K.B) P is
the effective permeability coefficient A is area of the skin JT is the total flux transported
through a unit area of skin per unit time in steady state (g/hr) Percutaneous absorption of

most drugs is a passive-diffusion process that can be described by Ficks first law of diffusion
dQ/dt = JT = PAC Skin permeability kinetics Ficks First Law of Diffusion
11. Formulation factors T.B.EKNATH 12 BABU (T.B.E.K.B) Biological factors Physicochemical
factors Factors affecting percutaneous absorption
12. Stability or half-life T.B.EKNATH 13 BABU (T.B.E.K.B) Molecular size and weight Ionization /
pKa Solubility Partition coefficient Physicochemical factors of penetrant/drug
13. Condition of the skin Integrity and Thickness of stratum corneum Pathological conditions of
skin Hydration Metabolism Temperature T.B.EKNATH 14 BABU (T.B.E.K.B) Age, Sex,
Race Area of application PH of the environment Biological factors
14. Composition of drug delivery system Surfactants T.B.EKNATH 15 BABU (T.B.E.K.B) Vehiclesolubility of the drug Lipophilicity of the solvent PH of the vehicle Formulation factors
15. Drug properties Dose deliverable : 10mg/day Aqueous solubility : >1mg/ml Lipophilicity : log P
(1-3) Molecular size : < 500 Daltons Melting point : < Along with these properties the drug should
be potent, having short half life T.B.EKNATH 16 BABU (T.B.E.K.B) The drug should not
stimulate an immune reaction in the skin. Drug should not be an irritant to skin. 200C
16. Strategies for the enhancement of drug permeability T.B.EKNATH 17 BABU (T.B.E.K.B)
17. Upon reaching the viable epidermis, esteras The prodrug design strategy generally involves
addition of a pro-moiety to increase partition coefficient and solubility to increase the transport of
the drug in the stratum corneum. The prodrug approach has been investigated to enhance
transdermal delivery of drugs with unfavourable partition coefficients. 1.Prodrugs Drug vehicle
interactions es release the active drug by hydrolysis thereby optimizing concentration in the
epidermis. T.B.EKNATH 18 BABU (T.B.E.K.B)
18. The ion-pair then dissociates in the aqueous viable epidermis releasing the parent charged drug
that can diffuse within the epidermal and dermal tissues. T.B.EKNATH 19 BABU (T.B.E.K.B)
This strategy involves adding an oppositely charged species to the charged drug, forming an ionpair in which the charges are neutralized so that the complex can partition into and permeate
through the stratum corneum. Charged drug molecules do not readily partition into or permeate
through human skin. Formation of lipophilic ionpairs has been investigated to increase stratum
corneum penetration of charged species. 2.Ion-pairs
19. Needle-free Jet Injectors T.B.EKNATH 20 BABU (T.B.E.K.B)
20. Intraject is a development of the vaccine gun designed to deliver liquids through skin without
using needles. The PowderJect system fires solid particles (20100m) through stratum
corneum into lower skin layers, using a supersonic shock wave of helium gas. Safety the
device avoids skin damage or infection from needles or splash back of body fluids. Accurate
dosing and Overcomes needle phobia. Targeting to a specific tissue, such as a vaccine
delivered to epidermal cells. Improved efficacy and bioavailability. Pain-free delivery
particles are too small to trigger pain T.B.EKNATH 21 BABU (T.B.E.K.B) receptors on the skin.
Advantages
21. Physically and Chemically compatible with a wide range of drugs. T.B.EKNATH 22 BABU
(T.B.E.K.B)Immediate recovery of normal barrier properties upon removal (reversible).
Immediate onset of increased permeability. Non-toxic, non-irritating, non-allergenic. A
substance that will increase the permeability of the epithelial barrier by modifying its structure
also termed as accelerants or sorption promoters-can enhance drug flux. Ideal Penetration
Enhancer 2.Chemical permeation enhancers

22. Solvents - Ethanol, acetone, polyethylene glycol, glycerol, propylene glycol, dimethyl sulfoxide
Surfactants - Brij30, brij72, Pluronic, Sodium lauryl sulphate, Span 20, Tween 80. Azones - NAcyl hexahydro-2-oxo-1H-azepines, T.B.EKNATH 23 BABU (T.B.E.K.B) N-Alkylmorpholine-2,3diones. Terpenes - Limonene, Carvone Fatty alcohols - Lauryl alcohol, linolenyl alcohol, oleic
and fatty acids acid and lauric acid. Miscellaneous - Lecithin, sodium deoxycholate, L-amino
acid, acid phosphatase,phospholipase & calonase
23. High-frequency ultrasound (310 MHz) - diagnostic purposes. T.B.EKNATH 24 BABU
(T.B.E.K.B) Low-frequency ultrasound (23-40kHz) - in dentistry, Therapeutic ultrasound (1
3MHz) - for massage, Sonicators operating at frequencies in the range of 20kHz to 3MHz are
available commercially and can be used for Sonophoresis. The ultrasonic energy (at low
frequency) disturbs the lipid packing in stratum corneum by cavitation. Used originally in
physiotherapy and sports medicine, applies a preparation topically and massages the site with an
ultrasound source. Electrically Assisted methods 1.Ultrasound (Phonophoresis / Sonophoresis)
24. Enhanced Transdermal Permeation by Cavitation of stratum corneum upon application of
Ultrasound. T.B.EKNATH 25 BABU (T.B.E.K.B)
25. Ultrasound to Enhance Skin Permeability T.B.EKNATH 26 BABU (T.B.E.K.B)
26. Electroosmosis may affect uncharged molecules and large polar peptides. Limitations: Hair
follicle damage is possible. T.B.EKNATH 27 BABU (T.B.E.K.B) Flow of electric current may
increase the permeability of skin and Charged species are driven primarily by electrical
repulsion from the driving electrode. The electrical driving of charged molecules into tissue,
passes a small direct current (approximately 0.5 mA/cm2) through a drug containing electrode in
contact with the skin. The most popular electrodes are based on the silver/silver chloride redox
couple. Three main mechanisms enhance molecular transport: 2.Iontophoresis
27. T.B.EKNATH 28 BABU (T.B.E.K.B)
28. This technology has been successfully used to enhance the skin permeability of molecules with
differing lipophilicity and size including biopharmaceuticals with molecular weights greater that
7kDA.. T.B.EKNATH 29 BABU (T.B.E.K.B) Skin electroporation (electropermeabilization)
creates transient aqueous pores in the lipid by application of high voltage of electrical pulses of
approximately 1001000 V/Cm for short time(milliseconds). These pores provide pathways for
drug penetration that travel straight through the horny layer. 3.Electroporation
29. T.B.EKNATH 30 BABU (T.B.E.K.B)
30. T.B.EKNATH 31 BABU (T.B.E.K.B)
31. T.B.EKNATH 32 BABU (T.B.E.K.B)
32. Other Excipients Rate controlling membrane Adhesive Release liner Backing membrane
T.B.EKNATH 33 BABU (T.B.E.K.B) Penetration enhancers Polymer matrix Drug Basic
components of TDDS
33. Types of Transdermal delivery devices T.B.EKNATH 34 BABU (T.B.E.K.B)
34. Transdermal matrix system 35 Rate controlling factors Drug concentration in polymer matrix
Chemical nature of polymer matrix Geometry of device Polymers: PVC, PVP, Ethylene
vinylacetate, microporous polypropylene. Initially the drug is released rapidly, then rate declines
as matrix is depleted. Advantages: Sleeker and thinner, daily or multiple-day Applications.
Appropriate for drugs that penetrate readily and/or have low dosage requirements.
35. Transdermal reservoir system 36 Rate controlling factors Membrane thickness Membrane
permeability Polymers: Cellulosic esters, polyamides or PVC. Advantages: Used when matrix

systems cannot penetrate skin and drugs require significant penetration enhancement and/or
high dosage levels.
36. They are occlusive and completely water impermeable in nature. e.g.: Poly urethane films, Ethyl
vinyl acetate, Poly ol They must be compatible with the formulation (nonadsorptive). They
have laminate structure. Contains formulation throughout shelf life and during wear period.
Provides low energy surface for ease of removal. e.g.: polyester or polystyrene based films.
Backing material Substrate carries a very thin release coating. Protects the skin-contacting
adhesive during storage. Release liners efins. Adhesive layer Acrylic copolymers,
polyisobutylene and polysiloxane. T.B.EKNATH 37 BABU (T.B.E.K.B)
37. Moisture absorption Mechanical properties Release liner peel, adhesion. Residual solvent,
residual monomer In vitro release Vs Ex vivo permeation of active and penetration enhancer
difussion cells. Content, Content uniformity. EEvvaalluuaattiioonn ooff TTDDDDSS & Pouch
integrity 38 T.B.EKNATH BABU (T.B.E.K.B) Microbiology Moisture loss
38. FFrraannzz DDiiffffuussiioonn CCeellll 39 T . B .E K SNkAiTnH: B RABaUt a(Tb.Bd.Eo.mK.Bin)
al, Rabbit, Porcine, Human cadaver
39. Mechanical properties eevvaalluuaattiioonn bbyy uullttrraa tteesstteerr 40 T.B.EKNATH BABU
(T.B.E.K.B)
40. Moisture aabbssoorrppttiioonn && Moisture absorption study: Saturated solution of Alcl3
(79.50% RH)/ 3 days. Moisture loss study: Patches were placed in a desiccator containing
Cacl2 at 40oC/24 hr. 41 T.B.EKNATH BABU (T.B.E.K.B)MMooiissttuurree lloossss
ssttuuddiieess
41. Transdermal patches available in the market T.B.EKNATH 42 BABU (T.B.E.K.B)
42. Marketed Products of Modified Transdermal Drug Delivery Technologies T.B.EKNATH 43 BABU
(T.B.E.K.B)
43. The market value for transdermal delivery was $12.7 billion in 2005, and is expected to increase
to $21.5 billion in the year 2010 and $31.5 billion in the year 2015 suggesting a significant
growth potential over the next 10 years. T.B.EKNATH 44 BABU (T.B.E.K.B) Advances in drug
delivery systems have increasingly brought about rate controlled delivery with fewer side effects
as well as increased efficacy and constant drug delivery. Transdermal drug delivery
technologies are becoming one of the fastest growing sectors within the pharmaceutical industry.
Conclusion
44. Asian Journal of Pharmaceutical and Clinical Research transdermal drug delivery system: a
review p. k.gaur,s. mishra, s. purohit, k. dave.. T.B.EKNATH 45 BABU (T.B.E.K.B)
Encyclopedia of controlled drug delivery volume 2 encyclopedia of controlled drug delivery
Controlled and Novel drug delivery edited by N.K.Jain reprint 2007 Encyclopedia of
pharmaceutical technology -third edition edited by James Swarbrick volume-4 Microsphere
Technology and Applications by Diane J. Burgess and Anthony J. Hickey. Controlled drug
delivery concepts and advances by S.P.Vyas R.K.Khar. References
45. Microneedles : The option for painless delivery by Geeta M Patel. T.B.EKNATH 46 BABU
(T.B.E.K.B) Transdermal drug delivery- penetration enhancement techniques- Heather A.E.
Benson. European Journal of Pharmaceutical Sciences Review -Novel mechanisms and
devices to enable successful transdermal drug delivery by B.W. Barry.
46. T.B.EKNATH 47 BABU (T.B.E.K.B)