TDDS

By Amina M. Al.nema

M.Sc. student

Mosul UniversityPharmacy College

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Introduction, advantages & disadvantages .

Skin : site of drug delivery.

Skin Anatomy , transport mechanisms.

Components of transdermal patches.

Generations of TDDS.

Recent Methods for enhancing permeation of TDDS

CONTENTS

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Transdermal drug delivery offers an attractive alternative to the oral administration and injection. Today about 74% of drugs are taken orally and are found not to be as effective as desired.

Drug delivery through the skin (for systemic effect ) is commonly known as TDD and differs from traditional topical drug delivery.

INTRODUCTION

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also known popularly as ‘patches’.

Transdermal patches: are dosage forms designed to deliver a therapeutically effective amount of drug from the outside of the skin through its layers into the blood stream.

INTRODUCTION

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ADVANTAGES1. avoids the stomach environment; 2. no GI distress or other physiological

contraindications of the oral route exist; 3. easy to use, patches can compliance & medical costs;4. avoids the first-pass effect;5. If a transdermal delivery system is used in place of a needle, then medical waste can also be , again, healthcare costs.

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ADVANTAGES

6. allows for the effective use of drugs with short biological half-lives;7. allows for the administration of drugs with narrow therapeutic windows; 8. provides steady plasma levels of highly potent drugs; 9. TDDS, especially simple patches, are easy to use and noninvasive and patients like noninvasive therapies.

7Steady plasma level of Ethinyl estradiol/norelgestromin

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DISADVANTAGES1. drugs that require high blood levels cannot be

administered; 2. The adhesive used may not adhere well to all

types of skin; 3. drug or drug formulation may cause skin

irritation or sensitization; 4. the patches can be uncomfortable to wear; 5. and this system may not be economical for

some patients.

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ADVERSE EVENTS FDA (2005) announced that fentanyl td patches cause narcotic overdose and deaths Cause: manufacturing defect that allowed the gel containing the medication to leak out of its pouch too quickly, which could result in overdose and death.

Improvement : use a matrix/adhesive suspension (where the medication is blended with the adhesive instead of held in a separate pouch with a porous membrane)

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CURRENTLY AVAILABLE DRUGS INCLUDE:

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SKIN SITE FOR TDDoThe human skin is a readily accessible surface for drug  delivery. oSkin of an average adult body covers a surface of ~ 2 m² and receives about 1/3 of the  blood circulating through the body.oHuman skin comprises of three distinct but mutually dependent layers :

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Microscopically skin is a multilayered organ broadly composed of three tissue layers :

The Epidermis The Dermis Subcutaneous fatty tissue.

SKIN ANATOMY

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SKIN ANATOMY

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Hairy skin develops hair follicles and sebaceous glands

The most important layer is the stratum corneum, or horny layer, which usually provides the rate-limiting or slowest step in the penetration process.

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TRANSPORT MECHANISMSPrinciple mechanism is passive diffusion of drug through the skin. macro-routes may comprise:a.Transepidermal pathway b. Transfollicular pathway

Hair follicle

Sebaceous gland Sweat

gland

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TRANSPORT MECHANISMS

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COMPONENTS OF TRANSDERMAL PATCHES

1- Backing,

2- Drug,

3-

Membrane,

4- Adhesive,

5- Liner.

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GENERATIONS OF TDDS

1. Liquid reservoir system where the patch consists of a backing material that is both protective and adhesive,a liquid drug reservoir, a release membrane.

2. Adhesive matrix system where the adhesive and the drug are

combined in the same layer leaving only three layers to the patch; the backing layer, the drug and adhesive layer, and the protective layer.

1st Generation

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Estraderm® Androderm® use the liquid-reservoir design

Most currently available patches are the adhesive matrix design.

1st Generation

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GENERATIONS OF TDDS

delivery of organic molecules by disrupting st. cor. barrier function by providing a driving force for the movement of molecules through the epidermis. This disruption should be reversible and avoid injury to the skin.

Enhancement techniques are limited to small, lipophilic molecules and still have little effect on larger or hydrophilic molecules.

2nd Generation

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Enhancement techniques include:1.chemical penetration enhancers,2. gentle heating,3. iontophoresis.

2nd Generation

GENERATIONS OF TDDS

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1 .Chemical Penetration Enhancers

METHODS FOR ENHANCING PERMEATION IN 2ND G.TDDS

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2 .Heat as a penetration enhancer

METHODS FOR ENHANCING PERMEATION IN 2ND G.TDDS

The use of heat to increase the permeability of the skin.One safe use of heat as a penetration enhancer is the Controlled Heat-Assisted Drug Delivery(CHADD) system.The lidocaine/tetracaine patch system.

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lidocaine/tetracaine patch

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The use of tiny electric current to promote flow of the drug (usually charged) through the skin.

METHODS FOR ENHANCING PERMEATION IN 2ND G.TDDS

3 .Iontophoresis as a 2nd G.penetration enhancer

Iontophoresis is a powered drug delivery system that is

indicated for the local administration of ionic drug solutions into the body for

medical purposes and can be used as an alternative to

injections .

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3 .Iontophoresis as a 2nd G.penetration enhancer

METHODS FOR ENHANCING PERMEATION IN 2ND G.TDDS

Self-contained, ultra-thin battery technology. Prepared by the clinician and applied to the patient in the clinic. With no external batteries or wires, patients are able to return to their daily activities while receiving time-released iontophoresis.

A charged drug delivery electrode (negative) repels the drug ions into theunderlying tissue.

WIRELESS PATCH

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GENERATIONS OF TDDS3rd Generation

3rd generation TDDS aim to severely disrupt the stratum corneum to allow large molecules to pass into the circulation.

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Human GnRH

METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

GnRH is not a small, organic compound but a

somewhat larger oligopeptide.

1 .Iontophoresis as a 3rd G.penetration enhancer

GnRH Smart Patch® iontophoretic technologyQuich, non-invasive, 10min. Application to skin.

METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

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METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

2 .Thermal ablation as a 3rd G.penetration enhancer

Thermal ablation technique seeks to severely disrupt the stratum corneum. 100s of degrees for very short periods of time (micro- to milliseconds) and forms painless, reversible microchannels in the stratum corneum without damaging the underlying tissue (2008).

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METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

3 .Ultrasound as a penetration enhancer

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METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

3 .Ultrasound as a penetration enhancer

Ultrasound to Enhance Skin Permeability

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Microneedle array consists of chips.

Used for adminstration of therapeutic proteins and vaccines.

METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

4 .Microneedle as a penetration enhancer

200-750 microns in length 150-650 microneedles/cm2

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METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

4 .Microneedle as a penetration enhancer

Poke and patch Method

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METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

4 .Microneedle as a penetration enhancer

Hollow micro needle array

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Intanza® is a seasonal flu vaccine that has been approved in Europe since 2009.

4 .Microneedle as a penetration enhancer

METHODS FOR ENHANCING PERMEATION IN 3rd G.TDDS

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Transdermal drug delivery technologies are becoming one of the fastest growing sectors within the pharmaceutical industry. Despite some disadvantages, transdermal drug delivery offers many advantages capable of improving patient health and quality of life. 1st and 2nd generation TDDS offer these advantages but are limited in the scope of moleculesdelivered through the skin.

CONCLUSION

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