A SEMINAR ON

TRANSDERMAL DRUG

DELIVERY SYSTEM

PRESENTED BY:

SHIRODE RAHUL A.rahulshirode2@gmail.com

M. Pharm.2nd sem.(2014-2015)

(Department of Pharmaceutics)

R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 1

CONTENTS Introduction

Advantages-Disadvantages

Comparison between IV, Oral and TDDS

Anatomy and Physiology of Skin

Permeation of Drug Molecule through Skin

Percutaneous Absorption

Classification of TDDS

Basic components of TDDS

Factors affecting Transdermal Permeation

Evaluation of TDDS

Application

Marketed Product

Conclusion

References.2

INTRODUCTION TDDS are topically administered medicaments in the

form of patches that deliver drugs for systemic effectsat predetermined and controlled rate.

Transdermal patch is an adhesive patch, that has acoating of medicine (drug), that is placed on the skinto deliver specific dose of the medicine, into theblood over a period of time.

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ADVANTAGES Avoidance of first-pass effect,

Long duration of action,

Comparable characteristics with IV infusion,

Ease of termination of drug action, if necessary,

No interference with gastric and intestinal fluids,

Suitable for administered of drug having-

Very short half-life, e.g. nitroglycerine.

Narrow therapeutic window.

Poor oral availability.

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DISADVANTAGES

Poor diffusion of large molecules,

Skin irritation,

Requires high drug load,

Unsuitable –If drug dose is large,

Absorption efficiency is vary with different sites of skin,

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COMPARISON BETWEEN IV,ORAL AND TDDSADVANTAGES IV ORAL TDD

Avoid hepatic

first-pass effects

YES NO YES

Constant drug levels

YES NO YES

Self-administration

NO YES YES

Termination of therapy

NO YES YES

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ANATOMY AND PHYSIOLOGY OF SKIN

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Skin is the part of Integrated system i.e. it helps tomaintain body temp and protect It fromsurrounding environment.

It covers an area of about 2m2 and 4.5-5 kg i.e. about16% of total body weight in adults.

Thickness is in range of 0.5mm (on eyelids ) to4.0mm ( on heels ).

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Skin has mainly 3 layers…

1)Epidermis

Stratum Cornium

Stratum Granulosm

Stratum Spinosum

Stratum Basal

2)Dermis

3)Subcutaneous layer

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EPIDERMIS Stratum Cornium- consists of 25 to 30 layers of

flattened dead keratinocytes. Which makes it waterrepellent.

Stratum Granulosm- consists of 3 to 5 layers andunder goes Apoptosis. It contains granules known asKeratohyalin. These granules release Lipid richsecretion, which acts as the water repellent.

Stratum Spinosum- contains 8 to 10 layers of cellsand it is closely arranged.

Stratum Basal- consists of single layer of cubical orcolumnar keratinocytes.

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DERMIS Composed of strong connective tissue containing

collagen and elastic fibres, hence it can easily stretchand recoil easily.

Blood vessel, nerves gland and hair follicles areembedded in this layer.

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SUBCUTANEOUS LAYER

It is also called as Hypodermis.

It is made up of loose connective tissue, includingAdipose tissue.

This helps to insulate the body by monitoring heatgain and heat loss.

The dermis is the layer of tissue that is Deeper andThicker than epidermis.

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PERMEATION OF DRUG MOLECULE THROUGH SKIN

It express by Fick’s first law of Diffusion-Drugmolecule diffuse from a region of higher conc. to oneof lower conc. until equilibrium is attained.

The process of Diffusion of molecule is driven bygradient between high concentration to lowconcentration.

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Fick’s First law of Diffusion-

dm/dt = J = D A K/h Where,

dm / dt =J= study state flux

D = diffusion coefficientA = surface areaK = partial coefficient between the Stratum

corneum and the vehicleh = diffusional path length or membrane

thickness

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PERCUTANEOUS ABSORPTION

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Percutaneous absorption done by 2-ways-

A. Transepidermal Absorption

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Stratum Corneum

Intracellular Pathway Intercellular Pathway

Viable Epidermis

Dermis

Microcirculation

B. Transfollicular Absorption

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Pilosebaceous unit Eccrine Gland

Hair Follicles Sebaceous Gland

Dermis

Microcirculation

CLASSIFICATION OF TDDS

A. Rate-Programmed Systems

Drug in Reservoir

Drug in Matrix

Drug in Adhesive

Drug in Microreservoir

B. Physical Stimuli-Activated Systems Structure-Based Systems Electrically-Based Systems

Iontophoresis Electroporation Sonophoresis

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1.Drug in Reservoir

2.Drug in Matrix

A.RATE-PROGRAMMED SYSTEMS-

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3.Drug in Adhesive

4.Drug in Microreservoir

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B. Physical Stimuli-Activated Systems-

1. Iontophoresis-

2. Electoporation-

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3. Sonophoresis-

4.Microneedles-

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BASIC COMPONENTS OF TDDS

Polymer matrix / Drug reservoir

Drug

Permeation enhancers

Pressure sensitive adhesive (PSA)

Backing laminate

Liner

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Polymer matrix / Drug reservoir-

Penetration Enhancers-

Chemical Enhancers-eg.- Azone, Pyrrolidone, Fattyacids, Essential oils, terpenes, organic solvents

Physical Enhancers-eg.- Iontophoresis, electroporation, Microneedles

Natural Polymer Synthetic Elastomer Synthetic Polymer

Gelatin Neoprene Polyethylene

Gum Arabic Silicone rubber Polystyrene

Starch Butyl rubber PVC

Shellac Chloroprene PVP

zein Polysiloxane Polyster

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Pressure Sensitive Adhesives (PSA)- A PSA is a material that helps in maintaining an intimate

contact between transdermal system and the skin surface.

Some widely used pressure sensitive adhesives are-

Eg- Polyisobutylenes, Polyacrylates, Silicones.

Backing Laminate:Hold and protect the drug reservoir from exposure to

atmosphere.Avoid loss of drugAccept printingHigh flexibilityEg- vinyl, polyethylene and polyester films, aluminium foil,

foam pad, metallic plastic laminate.

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Liner-

Protects the patch during storage. The liner is removedprior to use. Drug – Drug solution in direct contactwith release liner.

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FACTORS AFFECTING TRANSDERMAL PERMEATION

Physicochemical property of Drug molecule,

Partition co-efficient,

pH Condition,

Drug Concentration,

Molecular weight.

Physicochemical property of Drug DeliverySystem,

Release characteristics,

Use of permeation enhancer,

Composition of Drug Delivery System.27

Pathophysiological condition of Skin,

Reservoir effect of Horney Layer,

Hydration of skin,

Lipid Film,

Skin Temperature,

Pathological Injury to Skin,

Regional variation.

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Evaluation of TDDS

1. Evaluation of Adhesive

a. Peel Adhesion Properties- It is the force required to remove coating from a test substrate.

b. Tack Properties- It is the ability of polymer to adhere to a substrate with little contact pressure.

Thumb tack test

Rolling ball tack test

Quick-Stick test

Probe tack test

c. Shear Strength Properties- It is the measurement of the cohesive strength of an adhesive polymer.

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In vitro drug release evaluation

A. In vitro Permeation Studies-

In-Vitro skin Diffusion cells,

Skin-stripping,

Autoradiography.

B. In vitro Release Studies-

Paddle Over Disc Apparatus (USP Apparatus 5),

Reciprocating Disc (USP Apparatus 7).

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In vivo evaluation Animal models,

Skin-Stripping In vivo,

Microdialysis,

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APPLICATIONS For treatment of Angina Pectoris,

Smoking cessation(Nicotine Patch),

Contraceptive,

Antiemetic,

Anti-inflammatory,

Cosmetics.

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MARKETED PRODUCT

DRUG BRAND NAME MANUFACTURER

Nicotine Nicoderm gsk

Nicotine Habitraol Novartis

Nitroglycerine Transderm nitro Novartis

Insulin SonoDerm Imarx

Testosterone Testoderm Alza Corporation

Diclofenac diethyl amine NuPatch 100 Zudus Cadilla

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CONCLUSION

As we know, the basic functions of the skin isprotection and hence it is difficult to target the skinfor drug delivery. Because skin having numerouslayers. But using novel techniques in TDDS we havesuccessfully penetrate the drug into systemiccirculation.

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REFERENCES Brahmankar D. M., Jaiswal Sunil B.(2009)

Biopharmaceutics and Pharmacotherapeutics-ATreatise, 2nd edition, pp-495-501.

Chien Yie W.(2002), Novel Drug Delivery Systems,Marcel Dekkar, Inc Publication, volume-50, 2nd

edition, pp-301.

Walters Kenneth A.(2002), Dermatological andTransdermal Formulations, Marcel Dekkar, IncPublications, volume-119, pp-1,319.

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Robert’s Michael s., Walters Kenneth A.(2002),Dermal Absorption and Toxicity Assessment, MarcelDekker, Inc Publications, volume-91, pp-1, 189.

Dr. Patel Upendra, Bhavin Bhimani(2012)Transdermal Drug Delivery System As ProminentDosage Form For The Highly Lipophilic Drugs.International Journal Of Pharmaceutical ResearchAnd Bio-Science. Volume 1(3)42:65. pp- 1-6.

Jain, N.K. (1997) Controlled and novel drug delivery. 1st

ed. New Delhi: CBS publishers and distributors, pp.100- 127.

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