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TRANSDERMAL

DRUG DELIVERY SYSTEMS (PHYSICAL PERMEATION ENHANCERS)

“A review write up on several Physical Permeation Enhancers/Techniques in TDDS”

Worked by:

NIKHIL SUTAR

Re-edited by:

Suraj Choudhary

I – M.PHARM

DEPT. OF PHARMACEUTICS.

2013-14

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PHYSICAL PERMEATION ENHANCERS

1. Iontophoresis

2. Sonophoresis

3. Magnetophoresis

IONTOPHORESIS

A technique of introducing ionic medicinal compounds into the body through the skin by

applying a local electric current.

ADVANTAGES:

Virtually painless when properly applied.

Provides option for patients unable to receive injections. Reduced risk of infection due to

non-invasive nature.

Medications delivered directly to the treatment site. Minimizes potential for tissue trauma

from an injection. Treatments are completed in minutes.

LIMITATIONS: An excessive current density = pain.

Burns = by electrolyte changes within the tissues.

High current density & time of application→generate extreme pH →chemical burn.

Electric shocks may cause by high current density at the skin surface.

Ionic form of drug in sufficient concentration is necessary for iontophoretic delivery.

MECHANISM OF ACTION: Electrode placement depends on the electric charge of ion(drug) to be delivered into the

tissue.

Electrical energy assists the movement of ions across stratum corneum according to the basic

electrical principle- -“like charges repel each other & opposite charges attract each other.”

Here the choice of drug is very important whether it is ionized or unionized.

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+ve ion will be delivered from +ve electrode & -ve ion will be delivered by -ve electrode.

When -vely charged drug is to be delivered it is placed under -vely charged active electrode= it is repelled, attracted towards +ve electrode placed.

Iontophoresis enhances transdermal drug delivery by 3 mechanisms:

Ion-electric field interaction provides an additional force that drives ions through the

skin.

The flow of electric current increases the permeability of the skin.

Electro-osmosis produces bulk motion of solvent that carries ions or neutral species

with the solvent stream. Electro-osmotic flow occurs in a variety of membranes & is in

the same direction as the flow of counter-ions.

1. Passive Ionic Transdermal Drug Delivery System

Simple, relatively inexpensive & optimized enhancer patch system can accelerate the

delivery of larger electrically charged drugs.

Faster drug transport.

Enhanced safety.

More rapid onset of drug delivery.

2. Active Iontophoresis Transdermal Drug Delivery System

The application of external electric power source charges the drug substance; & facilitates

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movement of charged drugs to move into the skin.

Use of unique polymers to improve contact with skin & the rate and reliability of drug

delivery.

Use of stable & safe electrode materials for iontophoretic delivery.

Streamlined product design for ease of use & improved patient compliance.

More rapid onset of drug delivery.

Potential for better control over the rate of delivery.

Minimal skin irritation and enhanced safety.

COMPONENTS NEEDED FOR EFFECTIVE IONTOPHORESIS DELIVERY:

Power source for generating controlled direct current.

Electrodes that contain and disperse the drug.

Negatively or positively charged aqueous medication of relatively small molecule size

(<8000 Daltons).

Localized treatment site.

SELECTING THE APPROPRIATE ION:

1. Negative ions accumulating at the positive pole or anode:

Produce an acidic reaction through the formation of hydrochloric acid.

Produce softening of the tissues by decreasing protein density-useful in treating scars

or adhesions.

Some -ve ions can also produce an analgesic effect (salicylates).

2. Positive ions that accumulate at the negative pole:

Produce an alkaline reaction with the formation of sodium hydroxide.

Produce hardening of the tissues by increasing protein density.

TREATMENT PRECAUTIONS:

Patient has a good understanding of the existing condition which is to be treated.

Uses the most appropriate ions to accomplish the treatment goal. Uses appropriate

treatment parameters and equipment set-up.

FACTORS AFFECTING IONTOPHORETIC DELIVERY OF THE DRUG:

Operational Factors

I. Composition of formulation:

Concentration of drug solution

pH of donor solution

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Ionic strength

Presence of co-ions

II. Physicochemical properties of the permeant:

Molecular size

Charge

Polarity

Molecular weight

III. Experimental conditions:

Current density

Duration of treatment

Electrode material

Polarity of electrodes

Biological Factors

Regional blood flow

Skin pH

Condition of skin

APPLICATIONS:

1. Inflammation With Constant Pain (Red, Hot, and Swollen)

Dexamethasone Sodium Phosphate 0.4% (negative polarity) delivered from the cathode

for 3 treatments per week for 2-4 weeks.

Diclofenac 5% (negative polarity) delivered from the cathode for 3 treatments per week for

2-4 weeks.

Ketoprofen 10% (negative polarity) delivered from the cathode for 3-5 treatments per

week for 2-6 weeks.

Lidocaine Hydrochloride 4% (positive polarity) delivered from the anode for 3-5

treatments per week for 2 weeks.

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SONOPHORESIS

Sonophoresis is a technique which involves the use of ultrasonic energy to enhance skin

penetration of active substances.

Cavitation principle. 20kHz to168 kHz.

Transdermal enhancement is particularly significant at low frequency regimes (20 KHz < f

<100 KHz) than when induced by high frequency ultrasound.

Ultrasound parameters = treatment duration, intensity, pulse length & frequency are all

known to affect percutaneous absorption. Frequency being the most important.

MECHANISM OF ACTION:

Ultrasound produces thermal & non-thermal effects.

Due to this → formation of defects in stratum corneum of size 20 micron.

The mechanism of transdermal skin permeation involves the disruption of the stratum

corneum lipids by the formation of gaseous cavities, thus allowing the drug to pass through

the skin.

Example:

a) Sonophoresis of hypotensive agents & papain = treatment of eye diseases.

b) Several antibiotics = tetracycline, biomycin, penicillin have been sonophoretically

administered for the therapy of skin diseases.

c) Sonoprep (Sontra medical corporation). Local anasthetic.

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MAGNETOPHORESIS

Application of a magnetic field = acts as an external driving force to enhance drug delivery

across the skin.

Induces alteration in skin's structure that contribute to ↑ permeability.

Magneto-liposomes

Case Study:

Study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery

and also assessed the feasibility of designing a magnetophoretic transdermal patch system

for the delivery of lidocaine.

In vitro drug permeation studies were carried out across the porcine epidermis at different

magnetic field strengths.

The magnetophoretic drug permeation "flux enhancement factor" was found to increase with

the applied magnetic field strength.

The mechanistic studies revealed that the magnetic field applied in this study did not

modulate permeability of the stratum corneum barrier.

The predominant mechanism responsible for magnetically mediated drug permeation

enhancement was found to be "magnetokinesis".

The octanol/water partition coefficient of drugs was also found to increase when exposed to

the magnetic field.

A reservoir type transdermal patch system with a magnetic backing was designed for in vivo

studies.

The dermal bioavailability (AUC(0-6h)) from the magnetophoretic patch system in vivo, in

rats was significantly higher than the similarly designed non-magnetic control patch.