Iontophoresis is a non-invasive drug delivery system that uses a low-intensity electrical current to transport ionized drugs or other charged molecules through the skin. It has advantages over injections as it is painless, reduces risks of infection, and allows long-term medication through transdermal delivery. Key components needed are a power source to generate a direct current, electrodes to disperse the drug, and an ionized aqueous medication. Factors like current intensity, treatment time, drug properties, and skin properties affect the pharmacokinetics and delivery rate of iontophoresis. It has various biomedical applications for pain relief, dermatology, ophthalmology, and delivery of drugs like antihypertensives
2. INTRODUCTIONINTRODUCTION
Iontophoretic drug delivery is now an accepted method of
drug therapy which is gaining wide popularity especially in
the area of pain relief.
Non-invasive systemic administration of minute
amounts of drug transdermally which is especially useful in
patients who require long-term medication as in chronic
pain, diabetics, hypertensive, rheumatoid etc.
It negates the need for needle sticks, the pain and anxiety
involved and minimises the trauma and risks of infection
associated with it.
This mode of drug delivery is simple, versatile, effective,
reliable and can be tailored for individual needs.
3. DEFINITIONDEFINITION
"Iontophoresis is a process of transportation of ionic
molecules or drugs into the tissues or derma by passage of
electric current (0.5 mA/cm2
) through the electrolyte solution
containing the ionic molecules using a suitable electrode
polarity.“
This means it would involve an electromotive force
In the body, ions with a positive charge(+) are driven into the skin
at the anode and those with negative charge (-) at the cathode
Iontophoresis is sometimes confused with electrophoresis
IP involving movement of the colloid (dispersed phase)
EP involving the liquid (dispersion medium)
Iontophoresis may however cause an increased transport of method of
penetration of non electrolytes through tissues.
4. ADVANTAGESADVANTAGES
Virtually painless when properly applied.
Provides option for patients unable to receive injections.
Reduced risk of injection 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.
5. DISADVANTAGESDISADVANTAGES
An excessive current density usually results in pain.
Burns are caused by electrolyte changes within the
tissues.
The high current density & 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.
6. Iontophoresis enhances transdermal
drug delivery by three mechanisms
(a) Ion-electric field interaction provides an additional force that
drives ions through the skin.
(b) 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.
7. COMPONENTS NEEDED FOR EFFECTIVE
IONTOPHORESIS DELIVERY
Power source for generating controlled direct
current.
Electrodes and disperse the drug.
Negatively or positively charged aqueous medication
of relatively small molecule size (<8000 Daltons).
Localized treatment site.
8. PHARMACOKINETICS OF ION TRANSFERPHARMACOKINETICS 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.
9. IONTOPHORETIC DEVICES
Equipment should include safety, convenience, reliability
and reproducibility of the device.
Basic Components of the equipments
1. DC power supply
2. Milliammeter
3. Timer
4.Rheostat
5. 2 electrodes +ve and –ve charges
11. COMPONENT & SOURCECOMPONENT & SOURCE
Iontophoresis Generators - Produce continuous direct
current. Assures unidirectional flow of ions
Source of electrical energy = battery, supplies electric
current to the body through two electrodes.
The first electrode, called the donor electrode, delivers the
therapeutic agent into the body.
The second electrode, called the counter or receptor
electrode, closes the electrical circuit.
Each electrode contacts an ionically conductive
reservoir, normally present as a liquid or hydrogel.
The reservoirs are placed on the patient’s skin and contain
either the drug (for the donor electrode assembly)or a
biocompatible electrolyte (for the counter electrode assembly).
12. CONTROLSCONTROLS
Current 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.
• 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
Adjustable Timer Up to 25 min.
13. TREATMENT DURATIONTREATMENT DURATION
Treatment duration range =10-20 min with 15 min
average, increased as desired
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.
14. ELECTRODESELECTRODES
The electrode materials used for iontophoretic delivery are to
be harmless to the body & sufficiently flexible to
apply closely to the body surface.
The most common electrodes used for iontophoretic drug
delivery are
Aluminum foil
Platinum
Silver/Silverchloride
A better choice of electrode is silver/silver chloride
because it minimizes electrolysis of water during drug
delivery.
15. COMMERCIAL ELECTRODESCOMMERCIAL ELECTRODES
Sold with most iontophoresis systems.
Electrodes have a small chamber covered by a SPM into
which ionized solution may be injected.
The electrode self adheres to the skin.
19. MECHANISMMECHANISM
When applied topically, the current is applied through a
moist electrode
IP size depending on the skin region to be treated.
The drug is administered through an electrode (active) which
has the same charge as the drug.
This is very important; if the polarity of the electrode is not
the same as the ions, then penetration through the skin
may not occur.
The oppositely charged electrode (return) is placed some
distance away at a neutral site, the size and distance of the 2
electrodes would also affect the transport of ions.
Sweat ducts are primary paths by which ions move through
the skin.
20. MECHANISMMECHANISM
Current intensity < pain threshold that is comfortably tolerated by
the patient is passed for an appropriate length of time (< 5mA/cm2).
Current intensity should be gradually increased in the
beginning and slowly decreased towards the end.
The current can be given in any of the different waveforms, square,
sinusoidal, triangular etc. The current density is the current intensity
per unit cross sectional area. In practice, the density will vary from point
to point and the value calculated would be an average value at the
electrode surface.
The ions transferred through the skin are taken up by the micro-
circulation at the epidermo-dermal junction and the current
flows back through the return electrode. “like charges repel each“like charges repel each
other and opposite charges attract each other.”other and opposite charges attract each other.”
If any skin irritation occurs at this stage, the current intensity
should be lowered.
21. ADMINISTRATIONADMINISTRATION
To 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.
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.
Electrodes should be separated by at least the diameter
of active electrode. Wider separation minimizes
superficial current density decreasing chance for burns
22. 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
Charge
Polarity
Molecular weight
FACTORS AFFECTINGFACTORS AFFECTING
IONTOPHORESIS DRUG DELIVERYIONTOPHORESIS DRUG DELIVERY
23. III. Experimental conditions:
Current density
Duration of treatment
Electrode material
Polarity of electrodes
Biological Factors
Regional blood flow
Skin pH
Site & Condition of skin
Lipophilicity
Age
FACTORS AFFECTINGFACTORS AFFECTING
IONTOPHORESIS DRUG DELIVERYIONTOPHORESIS DRUG DELIVERY
24. FACTORS AFFECTINGFACTORS AFFECTING
IONTOPHORETIC DRUG DELIVERYIONTOPHORETIC DRUG DELIVERY
1. Ionised state of the drug: For eg. Lignocaine is not effective
iontophoretically at a ph range of 3.4-5.2. Iontophoresis transdermal
permission is maximum at pH of 9.4 and above when it is mainly in the
non-ionised state and at this pH, iontophoretic delivery is minimum.
2. Presence of extraneous ions: other ions of the some charge can
decrease the iontophoretic delivery of the drug ions because these ions
compete with the drug for the iontophoretic flux.
3. Ionic strength: Higher ionic strength of the solution subjected to
iontophoretic current resulted in decreased iontophoretic transport of
the drug into the tissues as increase in ionic strength yields higher
concentration of extraneous ions which compete for the electric current.
4. Concentration : increased concentration of the charged molecule yields
greater molecules in the tissues.
5. Current intensity: higher the intensity, greater then transport
25. Polarisation: Direct current can cause polarisation whilst pulsed
current can decrease tissue polarisation.
Shifts in pH in tissue and drug solutions: With metallic
electrodes, shifts in pH are noted which can affect ionisation of the
drug. pH changes in the tissue can use injury due to migration of
hydronium and hydroxyl ions produced by electrolysis. Separate
buffered electrolyte solutions can be used which can prevent flow of
ions into the tissue.
FACTORS AFFECTINGFACTORS AFFECTING
IONTOPHORETIC DRUG DELIVERYIONTOPHORETIC DRUG DELIVERY
26. BIOMEDICAL APPLICATIONBIOMEDICAL APPLICATION
Greatest advantage is in the transport of protein or peptide drugs which
are very difficult to transport transdermally due to their hydrophilicity
and large molecular size.
Dermatology
• In hyperhidrosis, especially palmar and plantar – probably by obstructing
the sweat ducts. No side effects when compared to anti- cholinergics.
• Copper- iontophoresis for fungal infection and male contraception, zinc
for ulcers, iodine for reduction of scar tissues,iron/titanium oxide for
tattoo removal.
• Histamine in allergy testing.
• In the diagnosis of cystic fibrosis to increase sweating by pilocarpine and
confirm diagnosis by the concentration of Na & Cl in the sweat.
• In scleroderma, iontophoretic delivery of hyaluronidase.
27. BIOMEDICAL APPLICATIONBIOMEDICAL APPLICATION
Ophthalmology : Iontophoretic induction of various drugs like
atropine, scopolamine, sulfadiazine, fluorescein, gentamycin etc
ENT For providing anaesthesia of the external ear canal and middle ear
and in maxillo facial prosthetics surgeries.
Dentistry To prevent dentin hypersensitivity and for providing local
anaesthetic for multiple tooth extraction.
Neurophysiological and Neuropharmacological studies
Micro-iontophoresis can be used to study neuro muscular junction,
peripheral and central nervous system and smooth muscle preparations.
Delivery of drugs
Antihypertensives, anti-diabetics, anti-rheumatoids, hormones,
vasodilators: Metaprolol, propranolol, insulin, methylcholine,
bleomycin, steroids have all been introduced iontophoretically.
Cardiology Iontophoretic transmyocardial drug delivery of anti-
arrhythmic drugs which would avoid high systemic toxic levels is being
done in animals.
28. BIOMEDICAL APPLICATIONBIOMEDICAL APPLICATION
For relief of pain
Iontophoretic histamine delivery as counter-irritant
In painless venipuncture
For post-operative pain relief
For iontophoretic delivery of local anaesthetics for referred pain
Anti-inflammatory drug delivery
Inflammation With Constant Pain (Red, Hot, and Swollen)Inflammation With Constant Pain (Red, Hot, and Swollen)
Dexamethasone Sodium PhosphateDexamethasone Sodium Phosphate 0.4% (negative polarity) delivered from the
cathode for 3 treatments per week for 2-4 weeks.
DiclofenacDiclofenac 5% (negative polarity) delivered from the cathode for 3 treatments
per week for 2-4 weeks.
KetoprofenKetoprofen 10% (negative polarity) delivered from the cathode for 3-5
treatments per week for 2-6 weeks.
Lidocaine HydrochlorideLidocaine Hydrochloride 4% (positive polarity) delivered from the anode for
3-5 treatments per week for 2 weeks
30. Lidosite®
- To deliver lidocaine, an anesthetic agent.
Phoresor®
II - To deliver botulinum molecule which
is used for the treatment of hyperhydrosis.
E-Trans® - To deliver fentanyl.
Phoresor® - To deliver iontocaine.
COMMERCIALLY DEVELOPED IONTOPHORETIC
DELIVERY SYSTEMS