Transdermal drug delivery systems by- Deepak kumar

1. Presented
-By
Guided by-
Dr.V.Kusum Devi

2.  Introduction
 Factors effecting permeation
 References
2
CONTENTS

3.  Transdermal drug delivery systems (TDDS) are systems that utilize skin
as a site for continuous drug administration .
 The main aim is to achieve systemic medication through topical
application to intact skin.
 TDDS is defined as a system, where the medicament leaves the
formulation and travels into the skin to provide its pharmacological action
when applied topically.
3
INTRODUCTION

4. I. Biological factors such as,
-Skin age
-Skin condition
-Regional site
-Skin metabolism
-Circulatory effect and species difference.
II. Physiological and pathological condition of skin like,
-reservoir effect of horny layer
-lipid film
-skin hydration
-skin temperature
-effect of vehicle
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FACTORS AFFECTING SKIN PERMEATION

5. III. Physicochemical property of drug molecule,
- Solubility and partition coefficient.
- pH condition
-Polarity
-Crystallinity and melting point
-Penetrant concentration.
-Molecular weight
IV. Physicochemical property of drug delivery system includes,
-Release characteristic
-Composition of drug delivery systems.
-Enhancement of Transdermal permeation.
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continued

6. a. Skin age:
 Skin of infants, young ones and elders are permeable than adult tissue.
 Children’s are more susceptible for skin toxic effect of drugs and other
additives in system.
b. Skin condition:
 Skin is tough barrier to penetration but only when it is intact. Many agents
can damage tissue thereby promotes permeation.
 Defective stratum corneum results in increase permeability 6
I. Biological Factors

7. c. Rational skin site:
 Diffusion is faster in scrotal, trunk, arm region when compare to palm or
foot.
d. Skin metabolism:
 Catabolic enzyme activity in viable epidermis is substantial.
 Infect the viable epidermis is metabolically active than dermis.
 If the topically applied drug is subjected to biotransformation during
skin permeation and systemic bioavailability can be affected markedly.
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8. e. Circulatory effects:
 Changes in peripheral circulation of blood flow through dermis could
effect percutaneous absorption.
 Thus an increased blood flow could reduce time for a penetrant
remains in dermis and so raise the concentration gradient across the
skin.
f. Species difference :
 Different species of mammalian skin display wide difference in
anatomy between common laboratory animals.
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9. a. Reservoir effect of horny layer:
 It is a deeper layer some times it acts as depot and modify Transdermal
permeation characteristics of drugs.
 Reservoir effect is due to irreversible binding of part of applied drug on
skin.
 This binding can be reduced by treatment of skin surface with anionic
surfactants.
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II. Physiological and pathological condition of skin

10. b. Lipid film:
 lipid film on skin surface act as protective layer to prevent removal of
moisture from skin and helps in maintaining barrier function of
stratum corneum.
 Defatting of this film found to increase Transdermal absorption.
c. Skin hydration:
 Enhances permeability, hydration can be achieved by covering or
occluding skin with plastic sheeting, increases hydration appear to
open up dense, closely packed cells of skin and increases its porosity.
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11. d. Skin temperature:
 It is directly proportional to the temperature.
 This is mainly due to
-Thermal energy required for diffusivity.
- Solubility of drug in skin tissue.
- Increased vasodilatation of skin vessels.
- Occlusion of skin surface increases the temperature by 2-3
centigrade result in increase molecular motion and skin permeation.
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12. e. Effect of vehicle:
 A vehicle can influence the percutaneous absorption by its potential
effect on physical states of skin.
 Ex: Grease, paraffin bases are most occlusive while w/o bases are less.
 Humectants in bases may dehydrate skin therefore decrease
percutaneous absorption.
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13. III. Physico-chemical property of the drug
molecules
a. Solubility and partition coefficient:
 Solubility of drug greatly influence on ability to penetrate in to skin.
 Partition coefficient which is the index of relative solubilization of drug
in vehicle and st. corneum has profound influence on transfer of drug
from vehicle in to skin.
 Drug solubility on the other hand determines con. of drug present on
absorption site., thus can effect rate and extent of drug absorption.
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14. Cont..
 The drug or vehicle partition coefficient roughly proportional to
relative solubility in stratum corneum and vehicle.
 Skin permeation can be increase by increasing lipophillic character of
drug, therefore drug having both lipid and water solubility are well
absorbed through skin.
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15. b. pH condition:
 Application of solution whose pH value are very high or very low can be
destructive to skin hence moderate pH favorable for drugs to penetrate
through skin.
 The flux of ionizable drugs can be affected by changes in pH that alters
the ratio of charged and uncharged species and their skin permeability.
c. Polarity:
 The polarity of a drug molecule affect its skin permeability by
imparting the partition co efficient
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16. d. Crystallinity and melting point:
 The concentration of drug in any medium is related to heat of fusion and
melting point.
 According to theory, the solubility of the drug is related to two important
thermodynamic parameter, heat of fusion and melting point.
 Hard crystalline material with enthalpies of fusion are less soluble than
soft, low melting compounds.
 Hydrophobic molecules generally have low degree of crystallinity and
owing to the very small net negative free energy of hydrophobic molecules
in water, therefore hydrophobic drugs are low solubility in water.
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17. e. Penetration concentration:
 Generally higher the con. Of dissolved drug in vehicle faster the
absorption.
 At concentration higher than the solubility excess solid drug function as
reservoir and helps to maintain a constant drug constitution for prolonged
period of time.
f. Molecular weight:
 Molecular weight of the drug molecules is another factor that affects its
ability to diffused across skin.
 The diffusion coefficient is a measure of diffusional resistance offered by
the membrane to any molecules and it related to the molecular size.
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18. a. Release characteristic:
 Solubility of drug in the vehicle determines release rate.
 The mechanism of drug release depends on,
-whether drug molecules are dissolve or suspended in delivery system.
-Interfacial partition coefficient of drug from delivery system to skin
tissue.
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IV. Physico-chemical properties of the
drug delivery system

19. b. Composition of drug delivery system:
 It not only affects the rate of drug release but also permeability of st,
corneum by means of hydration mixing with skin lipids or other
sorption promoting effects.
 Eg: Methyl salicylates is more lipophillic than its parent acid.
 When applied to skin from fatty vehicle, the methyl salicylates yielded
higher percutenous absorption.
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20. c. Enhancement of skin permeation:
 Permeation of most of the drugs can be improved by addition of
permeation enhancer in to the delivery system.
 Because majority of drugs will not penetrate through skin at rate
sufficiently high for therapeutic efficiency.
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21. Introduction to Novel drug delivery systems, first edition,
N.K.Jain.
Novel drug delivery systems, second edition Yie W Chein.
TRANSDERMAL DRUG DELIVERY SYSTEMS: AN OVERVIEW
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Thank
You…..--------------------------------------------------------------------------------