Penetration enhancer with their examples

Role of Penetration Enhancers in

Transdermal Drug Delivery System

Presented By:Ankita Rai

M. Pharm. II semester

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Flow of Presentation Introduction

Drug Delivery Routes Across Human Skin

Properties For Ideal Penetration Enhancers

Uses of Penetration Enhancers

Merits And Demerits of Penetration Enhancers

Classification of Penetration Enhancers

Physical Enhancers

References

VNS Group of Institutes

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INTRODUCTION

Penetration enhancers:Substances used to increase permeation of skin mucosa.

Increases the absorption of penetrant through the skin.

Synonyms: absorption promoter and sorption accelerants.


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Permeation occur by diffusion via1. Transdermal permeation through the

stratum corneum2. Intercellular permeation through stratum

corneum3. Transappendaged permeation via

a. hair follicleb. sebaceous glandsc. sweat glands

DRUG DELIVERY ROUTES ACROSS HUMAN SKIN


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Actions of penetration enhancers within the intercellular lipid domain


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DESIRABLE PROPERTIES FOR IDEAL PENETRATION ENHANCERS

Non-toxic, non-irritating and non-allergic

Rapid working

Predictable and reproducible duration of action

No pharmacological activity within the body

Work unidirectionally

When removed from the skin, barrier properties should return both rapidly and fully

Compatible with both excipients and drugs

Cosmetically acceptable


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1. To increase the delivery of ionisable drugs. Example: timolol maleate etc

2. To deliver the impermeable drugs. Example: heparin etc

3. To maintain level of drug into blood stream

4. To improve the efficacy of less potent drugs with higher dose. Example:

oxymorphane

5. To deliver the drugs having high molecular weight like peptide and hormones

6. To decrease lag time of transdermal drug delivery system

USES OF PENETRATION ENHANCERS


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Merits of Penetration Enhancers

1) Most drugs penetrate at rates sufficiently high for therapeutic efficiency by

using penetration enhancers

2) It is useful for unabsorbable drugs to facilitate their absorption through skin

3) It can improve transdermal absorption of topical preparation

4) No adverse effect on skin

5) Do not affect zero order skin permeation profile of skin

6) The terpenes like limonene in propylene glycol solution are effective

penetration enhancer for cytotoxic drugs


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1. The effective concentration varies from drug to drug

2. The uses of different penetration enhancer with various concentrations are

restricted completely

3. Physicochemical properties of enhancers are also affecting the side effects

in the body

Demerits of Penetration Enhancers


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PENETRATION ENHANCERS

Chemical enhancers

Physical enhancers

Drug vehicle based

Natural penetration

Miscellaneous

Biochemical approach

CLASSIFICATION

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CHEMICAL ENHANCERS

Mechanism of action:1. By distruption of highly ordered structure of stratum corneum lipid

2. By interaction with intercellular protein

3. By improved partition of the drug or solvent into stratum corneum

Examples:

Sulfoxide- DMSO, DMF, DMAC

Azones

Surface active agents- SLS, BKC

Amines & amides- urea

Fatty acids etcVNS Group of Institutes

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DRUG VEHICLE BASED PENETRATION ENHANCER

Mechanism of action :Interaction of enhancers with stratum corneum and development of SAR for

enhances with optimal characteristics and minimal toxicity.

Examples Ion pairs and complex Coacervates chemical potential adjustment.

Drug selection.


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NATURAL PENETRATION ENHANCERS

1. Terpenes- Menthol, Linalool, Limonene, Carvacrol

2. Essential oil-Basil oil, Neem oil, Eucalyptus oil

Mechanism of action :It may increase one or more of following effects

1. Partition coefficient

2. Diffusion coefficient

3. Lipid Extraction

4. Drug Solubility

5. Macroscopic Barrier Perturbation

6. Molecular Orientation of Terpenes Molecule

with Lipid Bilayer

Examples


VNS Group of Institutes 14

Physical Enhancers…


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1. Iontophoresis

• Iontophoresis is defined as “the application of a small electric current (0.5

mA/cm2 or less) with a low voltage, to drive ionic and polar molecules

across the skin and into the tissues”

• Used to deliver molecules such as neutral and charged molecules, low

and high molecular weight drugs namely phenobarbital, ranitidine and

zidovudine



Iontophoresis


2. Microneedle Array

MN arrays are composed of multiple micron-

sized projections which are typically assembled

on one side of a supporting base or patch

Length- 25μm to 2000μm

Therefore they can create little holes in the

stratum corneum without pain and become the

effective way to enhance the delivery of

therapeutic molecules and macromolecules

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3. Sonophoresis

Synonyms-Phonophoresis or Ultrasound

It involves the use of ultrasonic energy to

enhance skin penetration of active substances

Frequency range -20 KHz to 100 KHz

e.g. Drugs given are tetracycline, biomycin

and penicillin for skin diseases


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4. Magnetophoresis

Acts as an external driving force to enhance drug delivery across the skin

Induces alteration in the skin structure that could contribute to an increase in

permeability

e.g. Magnatoliposomes consisting of magnetic particles wrapped in

phospholipid bilayer which are applied for drug delivery, Magnetic resonance

imaging markers for cancer diagnosis

Mechanism of action :

Drug delivery across the membrane by the application of magnetic field


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5. Electroporation

• It involves the application of short, high

voltage pulses to skin

• Skin electroporation, also called

electropermeabilization, creates transient

aqueous pores in the lipid by application of

high voltage of electrical pulses of

approximately 100–1000 V/Cm for short

time (milliseconds)


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6. Thermophoresis

Thermal energy when applied to skin, cause increased skin

permeability

Heating during topical application of a drug dilates penetration

pathway in the skin and increase kinetic energy and movement of

particles in the treated area which facilitates drug absorption


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7. Radiofrequency

It involves exposure of the skin to a high frequency alternating current of 100

KHz that result in the formation of heat-induced microchannels in the cell

membrane.

Rate of drug delivery is controlled by number and depth of microchannels

formed which depends on the properties of microelectrodes in contact with the

skin during treatment.

e.g. Skin delivery of testosterone and growth hormones.


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• Permeability varies according to skin condition

• Hydrated skin is more permeable than dry skin

• Hydration of skin reduces resistance by loosening the

packaging of layers of stratum corneum

8. Hydration of stratum corneum


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Chemical peels- for superficial or light (epidermal), medium (epidermal–dermal

junction) or deep (deep papillary or papillary reticular dermis) treatments

Microdermabrasion which uses a stream of aluminium oxide crystals

Dermabrasion which employs a motor-driven abrasive fraise or cylinder

Laser ablation applies high- powered pulses to vapourise a section of the horny layer

Adhesive tape- To remove stratum corneum prior to drug application

A microinfusor device- To deliver peptides, proteins and other macromolecules

9. Stripping of stratum corneum

As the horny layer usually provides the permeation barrier, for

efficient drug delivery it can be removed by following techniques:


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1) Maghrabya, G. M. M. E., Michael, C., Barrie, C. F., 2005. International Journal of

Pharmaceutics 305, 90–104

2) Barry, B. W., 2001. European Journal of Pharmaceutical Sciences 14, 101 –114

3) Karande, P., Jain A., Ergun, K., Kispersky, V., Mitragotri, S., 2005. PNAS 102(13), 4688–

4693

4) Williams, A. C., Barry, B. W., 2012. Advanced Drug Delivery Reviews 64, 128–137

5) Gill, H.S., Prausnitz, M. R., 2007. Journal of Control Drug Release 117, 227–37

6) Henry, S., McAllister, D.V., Allen, M.G., Prausnitz, M. R., 1998. Journal of

Pharmaceutical Sciences 87, 922–925

7) Saini, S., Baghel, S., Agrawal, S. S., 2014. Journal of Advanced Pharmacy Education &

Research 4(1), 31-40

References

