Presentation 3

Introduction To Iontophoresis

DefinitionUsed forPhonophoresisComplicationsAdvantages over phonophoresis

Route Of Iontophoretic Drug DeliverySKINThe largest organ of the human body.Weight=about 15% of body weightSurface area=1.5 –2.0 square metersThickness=2-3mmSweat glands=650 average square inch of skinBlood vessels=20Melanocytes=60,000Nerve endings=more than a 1000

Diagram Of The Layers Of Human Skin

Mechanism Of Iontophoretic Drug Delivery Via Skin

o Skin consists ofo Lipids(15-20%)o Protiens(40%)o Approx. Water(40%)

o Patch Applicationo Alteration Of Molecular Rearrangemento Skin Permeability changeso Flip-Flop Gating mechanismo Isoelectric point of Skino Electro-osmosis

Principle Of Iontophoresis

Like & unlike charges

Negatively charged drug

Choice of drug

Compounds That Have Been Iontophoresed

Model Compound (s)

Indications and Applications

In vivo. Human

Morphine Postoperative analgesia

Metoprotol Hypertension

Lidocaine Skin puncture anesthesia Acyclovir Herpes orolabialis Penicillin Burn sterilization Fluoride Dentin hypersensitivity Hydrocortisone Arthritis Insulin Cystic fibrosis Tap water Hyperhidrosis

Compounds That Have Been Iontophoresed

Model Compound (s)

Indications and Applications

In vitro,excised skin

Propranolol Drug administration rate

Azidothymidine Iontophoresis enhancement

LHRH Skin peptide metabolism

Vasopressin Factors rate affecting delivery

Amino acids Factors affecting delivery rate

Piroxicam Drug administration rate

Factors Affecting Iontophoretic Transport

o General Factors likeo physiochemical properties of the compound o drug formulationo equipment usedo biological variationso skin temperatureo duration of iontophoresis.

Factors Affecting Iontophoretic Transport

o Current Strengtho Ionic Competitiono Drug Concentrationo Molecular Sizeo Convective Or Electro-

osmotic Transporto Current-continuous Vs.

Pulsed Modeo Physiological Factorso Influence of pH

Advantages

o Over Oral Administrationso Over Parenteral Therapyo Therapeutic Efficacy o Dosing o Short Biological Half-lifeo Simplified Therapeutic Regimeno Rapid Termination Of The Medication.

Disadvantages o Minor Reactions

o Long-lasting Skin Pigmentationo Need Of Aqueous Solution And Must Be

Ionizedo Limit To The Quantity-Usually more than 5 To

10 Mg/Hr Causes Burns To The Underlying Skin.

o Skin Itself A Barriero Isolated Report

Efficiency Of Iontophoretic Drug Delivery

The total iontophoresis current can be written as the product of electrode area A(cm2) and the current density id (mA/cm2). Thus,MD = ED ID A M W X t ZD x F

where MD = Dosage of the drugD (Quantity/time)F = Faraday's constant (96,500 coulombs/mole)ZD = Valence(Unitless) Mw = Molecular weight (g/moles)t = time (seconds)iD = current carried by drug ions.

 Hence this equation allows to calculate how much drug can be delivered by iontophoresis.

Iontophoretic Drug Delivery Device

An iontophoretic system has three basic components : the source of electric current- consists of a battery and control

electronics An active reservoir system- consists ionic therapeutic agent an indifferent or return reservoir system- contains an electrolyte

and serves to complete the electric circuit.

Vytris Iontophoretic PatchPositively charged drugs placed at the anode Return reservoir, placed at the cathode, which contains saline solution. A battery and microprocessor connect the anode and cathode reservoirs,

which are both in contact with the skin when the patch is applied.the current is switched on the positively charged drug molecules are forced away from the anode through the skin to the capillary bed below, in exchange for chloride ions At the cathode, chloride ions from the saline solution are forced away into

the capillary bed, and sodium ions are drawn up from the body fluid. For negatively charged drugs, the anode and cathode are reversed with respect to the drug reservoir and the return reservoir.Drug flux is proportional to current but is also dependent on the molecular

size and structure of the drug, its charge, the concentration of the drug, the presence of competing ions or permeation enhancers in the formulation, the area of the patch, and the integrity of the skin/patch interface.

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W/Alligator Clip Lead Wires Model Pm900c

Weight-4 oz Width-21/2” Length-41/2” Components-

Lead wires 9V alkaline battery Instruction guide

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Electrodes:No chemical buffers necessary Improve your drug delivery efficiency Deliver effective results in as few as three

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for easy-fill, no-stick handling. TransQ-1GS Active Area: 7.6 sq. cm

Fill Volume: 1.5 cc Max. Current: 4.0 mA Rec. Dosage: 24-40 mA-min Max. Dosage: 80 mA-min Skin Interface: GelSponge™ Conductor: Conductive Element

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Model 033 • Active Area: 11.2 cm 53 cm• Fill Volume: 2.5 cc N/A• Max. Current: 4.0 mA • Rec. Dosage: 40 mA-min

Max.• Dosage: 80 mA-min • Skin Interface: GelSponge™

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SilverChloride Carbon • Price $119.95

 Phoresor II Auto

Phoresor II Auto Safety And Convenience Features

• Description • Display Help • Automatic Time Calculation • Automatic Current Ramp Up • Automatic or Manual Current Ramp Down. • Pause • 10 Minute Automatic Shut Off • Resistance Limit • Dose and Current Limit • Electrode Reject

Setting Up The Phoresor II Auto

Preparing Electrodes And Patient For Treatment

NOTE : Please refer to directions for use supplied with electrodes for detailed instructions. DO NOT tape, bind or compress either electrode against the skin during treatment. Doing so may cause excessive skin irritation or burns.

Skin must be free of damage Preparation of drug electrode

For local Dermal Anesthesia For Other Medication

Preparation of skin sites Application of drug electrode Application of dispersive pad Attachment of twin lead connector clips

 Operating The Phoresor II Auto

Normally , a typical treatment requires only three steps :

Select dose Set current Start

treatment

In PIIA Selecting dose Setting current Starting current Pausing or stopping

treatment manually Stopping treatment

automatically After treatment

Duration And Intensity Of Current Faraday’s law.The time for iontophoresis ideally is 1 minute for

the increasing phase and 30 seconds for the decreasing phase. The intensity of the current used is between 40 mA and 10 mA regulated with a 25000 ohm potentiometer. Currents ranging from 5 to 10 mA have been found to be painless. The intensity of current should not exceed 0.5 to 1mA / cm2 for large electrodes.

Effects Of Current On The Body In the Frequency range of 10-200 Hz, the body

is most susceptible to the effects of current. To the exposed healthy canine heart, currents

as low as 20 mA ( 60 Hz rms) can cause fibrillation .

Current greater than 2A can cause temporary cardiac arrest and paralysis.

Current greater than 6A can cause cardiac arrest, paralysis and deep burns.

Optimising Iontophoretic Transport

Variation in applied current density and area of application

pH optimizationCleaning of skin area

Contraindications for lontophoresis

Contraindications for iontophoresis are important in patients with higher susceptibility to applied currents. Such patients include those carrying electrically- sensitive implanted devices such as cardiac pacemakers, those who are hypersensitive to the drug to be applied, or those with broken or damaged skin surfaces.

In-vitro Evaluation

In-vivo Evaluation

Morimoto et al. (1992) described an in-vivo iontophoretic system used in rats for transdermal iontophoretic delivery of vasopressin and analogue in rats. A hypotonic solution was administered through the femoral catheter as a constant infusion. Two cylindrical polyethylene cells were attached to the abdominal skin of the rat. A pair of Ag/AgCI electrodes was immersed in the solutions, the anode being in the drug solution and thej;athode in the 0.9% w/v NaCl solution. The electrodes were connected to a constant current power sourcfe.

CONCLUSION: Iontophoresis involves delivery of selected ions into tissues by

passing a direct electrical current through a medicated solution and the patient.

This method of drug administration has many advantages Systemic side effects of drugs are significantly decreased because

only minute amounts of drugs are delivered, while a relatively high drug concentration is administered locally where it should achieve the maximum benefit.

Patient acceptance is generally excellent and fear of injection is eliminated. Thus, iontophoretic transdermal delivery has the potential of improving the quality of drug therapy compared to conventional methods of oral drug administration or bolus intravenous injection because it can minimize dosage while maintaining a constant therapeutic level by continuous drug input.

Scope For Future Work 1.Development of an ideal membrane, and an

animal model.2.Development of a foolproof method of measuring

skin resistance, and feedback of the electrical parameters to the device being used, which can adjust the drug delivery rate accordingly.

3. Miniaturization and cost-reduction of the device.4.Mathematical models to extrapolate the results of

animal experiments to clinical situations.