IONTOPHORESIS: TRANSDERMAL DRUG DELIVERY

Guided by,

Professor Kurian Varghese & Asst.Professor Dinu Thomas

Submitted by, Amrith Vijay V L S7 EEE Rollno-8

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CONTENTSCONTENTS INTRODUCTION PRINCIPLES OF IONTOPHORESIS ADVANTAGES OF IONTOPHORESIS COMPLICATIONS IN IONTOPHORESIS IONTOPHORESIS DIAGRAM THREE MECHANISMS OF IONTOPHORESIS IONTOPHORETIC GENERATOR TREATMENT DURATION & PRECAUTION CONCLUSION REFERENCES

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Introduction

• The term IONTOPHORESIS simply defined as ion transfer (ionto= ion & phoresis=transfer).

• It is a Painless, Sterile, Noninvasive Technique for injecting medicine to the body by the influence of electricity.

• 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.” So iontophoresis is done with the help of electrostatic repulsion.

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Advantages of Iontophoresis

• Painless technique if properly done.

• 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.

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 Complications in iontophoresis

• Electric shocks may cause if excessive current density occurs & usually results in pain.

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

• Iontophoresis cannot be done to patients with cardiac pacemakers.

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

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IONTOPHORESIS DIAGRAM

Figure showing transdermal drug delivery by iontophoresis

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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 or neutral species 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. It may assist or hinder drug transport.

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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.

• A localized treatment site.

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Movement of Ions In Tissue

Higher current intensities necessary to create ion movement in areas where skin and fat layers are thick, further increasing chance of burns around negative electrode.

Sweat ducts are primary paths by which ions move through the skin.

Once the ions pass through skin they recombine with existing ions and free radicals in the blood thus forming the necessary new compounds for favorable therapeutic interactions.

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Iontophoresis Generator

Produce continuous direct current in the order as per the requirement.

Assures unidirectional flow of ions.

It also consist of a timer for regulating the supply of current.

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Intensity control• 1 to 5 mA• Constant voltage

output that adjusts to normal variations in tissue impedance thus reducing the likelihood of burns.

• Automatic shutdown if skin impedance reduces to preset limit.

Adjustable Timer for giving the duration of treatment

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Current Intensity• CI can be found out by

Maximum current(mA)= Maximum Safe Current Density(mA/cm2) x Electrode Area(cm2)

• Recommended current intensity used for iontophoresis ranges between 3-5 mA

• Low amperage currents appear to be more effective as a driving force than currents with higher intensities (16 to 512μA)

• The frequency of current should be in the range of 500 Hz to avoid shock hazards

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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.

Usage of pulsed DC can be reduce the duration of treatment 14

Treatment Precautions

Uses the most appropriate ions to accomplish the treatment goal

Uses appropriate treatment parameters and equipment set-up

Don’t use two chemicals under the same electrode even if the they are of same polarity

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Electrodes of iontophoresisActive pad- This electrode have

a small chamber covered by a semipermeable membrane into which ionized solution may be injected.

Dispersive pad- Also known as Inactive pad. Dispersive pad should be larger than active pad to reduce the current density leading to reduction of irritation

The polarity of these electrode

depends on the characterictics of drugs and these electrodes self adheres to the skin.

Active pad

Dispersive pad

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Iontopatch

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Electrodes Material

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

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Electrode PreparationTo ensure maximum contact of

electrodes skin should be shaved and cleaned prior to attachment of the electrodes.

Do not excessively abrade skin during cleaning since damaged skin has lowered resistance to current and a burn might occur more easily.

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• Attach self-adhering active electrode to skin.

• Inject ionized solution into the chamber.

• Attach self-adhering inactive electrode to the skin and attach lead wires from generator to each.

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Electrode Placement

• Size and shape of electrodes can cause variation in current density (smaller = higher density)

• Inactive electrodes should be separated by a distance atleast the diameter of active electrode

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Factors Affecting Iontophoretic Delivery of the Drug

Operational Factors

I. Composition of formulation:

• Concentration of drug solution

• pH of donor solution

• Ionic strength

• Presence of co-ions

II. Physicochemical properties of the permeant:

• Molecular size & Molecular weight

• Charge

• Polarity

III. Experimental conditions:

• Current density

• Duration of treatment

• Electrode material

• Polarity of electrodes Biological Factors

• Regional blood flow

• Skin pH

• Condition of skin

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Formula for iontophoresis:

The basic formula for using iontophoresis is:          I x T x ECE = grams of substance introducedWhere: I: (Intensity) measured in amperes. T: (Time) measured in hours. ECE: (Electro-Chemical Equivalent) represents standardized

figures for ionic transfer with known currents and time factors.

As the determination of the ECE for many complex substances is very difficult, fewer milligrams of these complex substances will penetrate the skin.

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Conclusion

Iontophoretic drug delivery has developed a newapplication 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• Iontophoretic transport kinetics of ketorolac in vitro and in vivo:

Demonstrating local enhanced topical drug delivery to the muscle. T. Gratieri, E. Pujol-Bello, G. M. Gelfuso, J. G. de Souza, R. F. V. Lopez, Y. N. Kalia. Eur J Pharm Biopharm, 2014; 86: 219-226

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

• 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 .

• Turning theory into practice: the development of modern transdermal drug delivery systems and future trends. O. Perumal, S. N. Murthy, Y. N. Kalia. Skin Pharmacol Physiol, 2013; 26: 331-342

• Controlled iontophoretic transport of huperzine A across skin in vitro and in vivo: effect of delivery conditions and comparison of pharmacokinetic models. D. R. Kalaria, P. Patel, V. Merino, V. B. Patravale, Y. N. Kalia. Mol Pharm, 2013; 10(11): 4322-4329.

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