IONTOPHORESIS /Introduction PPT/PDF

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Description

IONTOPHORESIS

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Introduction

Iontophoresis is a non-invasive method of propelling high

concentrations of a charged substance, normally medication or

bioactive agents transdermally by repulsive electromotive force

using a small electrical charge approximately (0.5 mA/cm2)

applied to an iontophoretic chamber containing a similarly

charged active agent and its vehicle.

• It is a Painless, Sterile, Noninvasive Technique

• Iontophoresis is well classified for use in transdermal drug

delivery.

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Principles of Iontophoresis

• Electrode placement is dependent on the electric charge of the
ion which you are trying to deliver into the tissue.

 

• A positive ion will be delivered from the positive electrode and
a negative ion will be delivered by the negative electrode.

 

• Electrical energy assists the movement of ions across the
stratum corneum according to the basic electrical principle
“like charges repel each other and opposite charges attract
each other.”

 

 

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Iontophoresis Diagram

B)
A)

B)

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Mechanism
• Skin Consist of Lipids (15-20%), protein(40%) and water (40%).

1. Flip flop gating mechanism – model for voltage dependent pore

formation in stratum corneum.

• Electric potential produces molecular rearrangement increasing

permeability.

• Electric field change chemical potential of molecules in skin and

provide sufficient energy to make confirmational changes which

facilitates the entry of ions.

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2. I.P. of skin is 3-4.

• It has +ve charge below pH 3 and – ve charge above pH 4.

• Superficial skin layer has net negative charge.

• Delivery of basic drugs above pH 4.

 

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3. Electro osmosis – transport of liq. Water as a whole can interfere

with the mechanism of iontophoresis.

This causes the migration of undissociated molecules in the solution.

Because the skin has –ve charge, iontophoresis will effect movement

of water into the body from +ve pole iontophoretically towards

the outer surface of the skin at the –ve pole and cause the swelling

at the – ve pole after intense iontophoresis. The process is helpful

in case of cation transfer from the positive pole, as it acts in the

same direction, facilitating absorption of cationic drugs. E.g.

iodoxuridine sodium

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Iontophoresis enhances transdermal drug
delivery by three mechanisms

(a) ion-electric field interaction provides an additional force
that drives ions through the skin.

 

(b) the flow of electric current increases the permeability of
the skin.

 

(c) electro-osmosis produces bulk motion of solvent that
carries ions with the solvent stream. Electro-osmotic flow
occurs in a variety of membranes and is in the same
direction as the flow of counter-ions.

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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.

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Iontophoresis Generators

Produce continuous
direct current.

Assures unidirectional
flow of ions.

 

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Current Intensity control

• Low amperage currents appear to be more effective as a driving
force than currents with higher intensities.

• Higher intensity currents tend to reduce effective penetration
into the tissues.

• Recommended current amplitudes used for iontophoresis range
between 3-5 mA.

Constant voltage output that adjusts to normal variations in

tissue impedance thus reducing the likelihood of burns.

Adjustable Timer

Up to 25 min.

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Electrodes

The electrode materials used for iontophoretic delivery are
to be harmless to the body and sufficiently flexible to apply
closely to the body surface.

The most common electrodes used for iontophoretic drug
delivery are

 Aluminum foil

 Platinum and

 Silver/Silverchloride

A better choice of electrode is silver/silver chloride
because it minimizes electrolysis of water during drug
delivery.

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Commercial Electrodes
 Sold with most iontophoresis systems.
 Electrodes have a small chamber covered by a semipermiable

membrane into which ionized solution may be injected.
 The electrode self adheres to the skin.

Either +ve or – ve ions of drug are delivered.
Skin site with proper conditions are selected to avoid any
pain or burn to patient.

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PHARMACOKINETICS OF ION TRANSFER

• Transdermal iontophoresis delivers medication at a
constant rate so that the effective plasma concentration
remains within a therapeutic window for an extended
period of time.

 

 Therapeutic window – the plasma concentrations of a
drug which should fall between a minimum
concentration necessary for a therapeutic effect and
the maximum effective concentration above which
adverse effects may possibly occur.

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Treatment Duration

 Treatment duration ranges between 10-20
minutes with 15 minutes being an average.

 Patient should be comfortable with no reported or visible

signs of pain or burning.

 Check skin every 3-5 minutes looking for signs of skin

irritation.

 Decrease intensity during treatment to accommodate

decrease in skin impedance to avoid pain or burning.

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Factors Affecting Iontophoretic Delivery of the
Drug

 Operational Factors

I. Composition of formulation: III. Experimental conditions:

• Concentration of drug solution • Current density

• pH of donor solution • Duration of treatment

• Ionic strength • Electrode material

• Presence of co-ions • Polarity of electrodes

II. Physicochemical properties of  Biological Factors

the permeant: • Regional blood flow

• Molecular size • Skin pH

• Charge • Condition of skin

• Polarity

• Molecular weight

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Advantages of Iontophoresis

• 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.

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• Prevents variation in absorption and metabolism of oral
administration.

• Increases therapeutic efficacy by bypassing first pass
metabolism.

• Reduces chance of over or under dosing by continuous
delivery of drug programmed at the required therapeutic
rate.

• Permit the use of drugs with short biological half life.

• Provides a simplified therapeutic regimen increasing patient

compliance.

• Permits a rapid termination of the medication, if needed, by

simply stopping the drug input from the iontophoretic

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problems by iontophoresis

• An excessive current density usually results in pain.

• Burns are caused by electrolyte changes within the
tissues.

• The high current density and time of application would
generate extreme pH, resulting in a chemical burn.

• This change in pH may cause the sweat duct plugging
perhaps precipitate protein in the ducts.

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

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

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• Many parentrally administered drugs are supplied

with admixtures of NaCl, sodium citrate etc. usually

for the purpose of rendering them isotonic. These

additional ions act as charged carriers or active

competitors for the drug applied..

• Limit of quantity of medication that can be

delivered.(10mg) if want to exceed would require a

current sufficiently high to cause burn to underlying

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Commercially developed iontophoretic
delivery systems

• Lidosite®- To deliver lidocaine, an anesthetic agent.

 

• Phoresor® II – To deliver botulinum molecule

 

• E-Trans® – To deliver fentanyl.

 

• Phoresor® – To deliver iontocaine.

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Applications
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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Conclusion

Iontophoretic drug delivery has developed a new
application system for dermal and transdermal delivery of
drugs that is electro-phoretically self-regulated device with
electronic indicator.

The iontophoretic delivery of macromolecules will open
the doors to non-invasive transdermal delivery of peptide-
based pharmaceuticals.

Iontophoresis has been explored for many dermatologic
and other medical conditions with reports of considerable
success.

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REFERENCES
• Anderson CR, Morris RL, Boeh SD, et al. “Effects of iontophoresis current magnitude and

duration on dexamethasone deposition and localized drug retention.” Phys Ther. 2003;
83:161-171.

• Artusi, M.; Nicoli, S.; Colombo, P.; Bettini, R.; Sacchi, A.; Sanli,P. J. Pharm. Sci. 2004, 93
(10), 2431-8.

• Banga, A.K. Electrically assisted transdermal and topical drug delivery, Taylor and Francis,
London, 1998.

• Banga, A.K.; Chien, Y.W. J. Control. Release, 1988, 7(1), 1-24.
• Banga, A.K.; Bose, S.; Ghosh, T.K. Int. J. Pharm. 1999, 179(1), 1-19.
• Bertolucci, L.E. “Introduction of Anti-inflammatory Drugs by Iontophoresis: Double Blind

Study.” J Orthopedic and Sports Physical Therapy. 1982;4:103-108 .
• Chou, W.-L.; Cheng, C.-H.; Yen, S.-C.; Jiang, T.-S. Drug Dev. Ind. Pharm. 1996, 22(9&10),

943-50.
• Clemessy, M.; Couarraze, G.; Bevan, B.; Puisieux, F. Int. J. Pharm. 1994, 101(3), 219-26.
• Garzione, John E. PT,DPT, D.A.A.P.M. Alternative Compounds and Advances in

Iontophoresis. 20 June 2006. Sturm. Overuse injury [article]. Available
at: http://www.emedicine.com/pmr/topic97.htm. Accessed July 10, 2006.

• Harris PR. “Iontophoresis: Clinical Research in Musculoskeletal Inflammatory Conditions.” J
Ortho Sports PT. 1982;4:109-112.

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