TRANSDERMAL DRUG DELIVERY SYSTEM

Deepak Kumar

Presented-By

Guided by- Dr.V.Kusum Devi

2

Introduction

Factors effecting permeation

References

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.

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   

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.

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

 

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.

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.

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.

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.

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.

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.

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.

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.

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

 

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.

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.

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.

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.

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.

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

22

Thank You…..

--------------------------------------------------------------------------------