Presentation 3

Introduction To Iontophoresis  Definition  Used

for  Phonophoresis  Complications  Advantages over phonophoresis

Route Of Iontophoretic Drug Delivery SKIN The largest organ of the human body. Weight=about 15% of body weight Surface area=1.5 –2.0 square meters Thickness=2-3mm Sweat glands=650 average square inch of skin Blood vessels=20 Melanocytes=60,000 Nerve endings=more than a 1000

Diagram Of The Layers Of Human Skin

Mechanism Of Iontophoretic Drug Delivery Via Skin o

Skin consists of

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

Patch Application o Alteration Of Molecular Rearrangement o Skin Permeability changes o Flip-Flop Gating mechanism o Isoelectric point of Skin o Electro-osmosis o

Principle Of Iontophoresis  Like

& unlike charges  Negatively charged drug  Choice of drug

Compounds That Have Been Iontophoresed Model Compoun Indications and d (s) Applications In vivo. Morphine Postoperative analgesia Human 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 Indications and (s) Applications

In vitro,excised Propranolol skin

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 like o o o o o o

physiochemical properties of the compound drug formulation equipment used biological variations skin temperature duration of iontophoresis.

Factors Affecting Iontophoretic Transport o o o o o o o o

Current Strength Ionic Competition Drug Concentration Molecular Size Convective Or Electroosmotic Transport Current-continuous Vs. Pulsed Mode Physiological Factors Influence of pH

Advantages o o o o o o o

Over Oral Administrations Over Parenteral Therapy Therapeutic Efficacy Dosing Short Biological Half-life Simplified Therapeutic Regimen Rapid Termination Of The Medication.

Disadvantages o Minor Reactions o Long-lasting Skin Pigmentation o Need Of Aqueous Solution And Must Be Ionized o Limit To The Quantity-Usually more than 5 To 10 Mg/Hr Causes Burns To The Underlying Skin. o Skin Itself A Barrier o 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, M D = ED I D 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 t iD

= = =

Molecular weight (g/moles) time (seconds) 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 Patch Positively

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.

ALZA

W/Alligator Clip Lead Wires Model Pm900c  Weight-4

oz  Width-21/2”  Length-41/2”  Components  

Lead wires 9V alkaline battery Instruction guide

Transq-1gs (6 Kits) Model 031 Top reasons to choose TransQ® Electrodes: No chemical buffers necessary Improve your drug delivery efficiency Deliver effective results in as few as three treatments—fewer treatments mean more efficient service delivery Convenient peel-away window provides 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 Price $59.95

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™ Carbon Conductor: SilverSilverChloride 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 optimization Cleaning 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.