Asian American Pacific Islander Month DDSD 2024.pptx
Iontophoresis
1. IONTOPHORESIS
(drug delivery system)
By,
Dr. Shreeraj Shah
Associate Professor,
Dept. of Pharmaceutical
Technology,
L. J. Institute of
Pharmacy, Ahmedabad
1
2. content
Introduction
Advantages and disadvantages
Electrical property of skin
Route and mechanism of system
Factor affecting iontophoresis
Equipments and devices
Evaluation
Application
2
4. HISTORICAL DEVELOPMENT:-
The idea of applying electric current to
increase the penetration of electrically charged
drugs into surface tissues was probably
originated by varatti in 1747.
Ledus demonstrated the introduction of
strychnine and cyanide ions in to the rabbits at
the beginning of the 20th century , placing two
rabbits in series with a direct current
generator.
Today, the treatment of hyperhidrosis is the
most successful and popular application of
iontophoresis in dermatologic medication.
4
5. Advantages
Enhanced drug penetration (of selected drugs)
over passive transport .
Allows strict control of transdermal penetration
rates.
Permits rapid termination of drug delivery
through termination of current or ultrasound.
Skin remains intact, therefore low risk of
introducing infection .
Not immunologically sensitizing.
In many cases, greater patient satisfaction.
Home units available for iontophoresis.
5
6. Advantages over other delivery system
Iontophoresis enlarges the range of drug
candidates for transdermal administration.
Fast skin recovery than parentral route.
Less risk of systemic absorption than
injection.
Less anxiety provoking or painful than
injection
Increases therapeutic efficacy by bypassing
hepatic “first pass” metabolism.
Inter and intra subject variability is
considerably reduced in contras to oral
route.
6
7. Disadvantages
Can be time-consuming to administer
Drugs must be in aqueous solution and must
be in ionized.
Minor tingling, irritation, and burning can
occur. (these effects can often be minimized
or eradicated with proper technique or
current adjustment ).
The skin itself imposes a barrier to the
delivery of some medication.
Additional ions act as charged carriers or
active competitors for the drug applied.
7
8. Electrical property of the skin
Stratum corneum is composed of layers of horny
cells which are a good insulator and forms the
principal barrier of the body to electrical
conductivity.
In addition to electrical resistance, skin tissue also
have a capacitance because of their ability to store
electrons, and are thus electrically capacitors, so
skin layer is said to be reactive. A reactive circuit is
said to be present impedance rather than
resistance.
The human skin reportedly shows a high
impedance to alternating current of low frequency,
but the impedance was found to decrease from
130 to 30 kilo ohm as the A.C input was increased
from 1 to 1000 Hz.
8
10. Route and mechanism of system
The greatest concentration of ionized species is
expected to move into some regions of the skin
where either the skin is damaged ,or along the
sweat glands and hair follicles, as the diffusional
resistance on the skin to permeation is lowest in
these regions.
10
11. Pathway of ion transport
Percutaneous absorption may take place
simultaneously by any combination of the
three main pathways that include; the
intercellular (paracellular) pathway
between the conneocytes along the lamellar
lipids, the intracellular (transcellular)
pathway through the cells or the
appendageal (shunt) pathway via hair
follicles, sweat ducts and secretary glands.
11
12. T.S. of SKIN
Fig. 1. A diagrammatical representation of human skin:
(a) appendageal pathway; (b) intercellular pathway.
12
13. Mechanism:-
In iontophoretic treatment electric potential
may alter the molecular arrangement of the
skin components hence change in skin
permeability.
The “flip-flop gating mechanism” could be
responsible for pore formation in the stratum
corneum which is rich in keratin, an alpha-
helical polypeptide.
13
14. Pores are thus opened up as a result of
repulsion between neighboring dipoles,
and water molecule and ions will flow in
the pore channels to neutralize the dipole
moments. The phenomenon should lead
to an enhancement in skin permeability for
peptide and protein molecules, and other
charged molecules.
The isoelectric point of the skin is
between 3 and 4,means pores have
positive charge below pH 3 and negative
charge below pH 4 ,so it is easy to
introduce basic drug. 14
15. Movement of Ions In Solution
Ionization- Soluable compounds dissolve
into ions suspended in solutions that are
called electrolytes
Electrophoresis- Movement of ions in
solution according to the electrically
charged currents acting on them.
To understand this….
Understanding of Cathode and Anode
15
16. Movement of Ions In Solution
Cathode = Negatively charged electrode
♦Highest concentration of electrons
♦Repels negatively charged ions
♦Attracts positively charged ions
♦Accumulation of positively charged ions in a
small area creates an alkaline reaction
16
17. Movement of Ions In Solution
Anode = Positively charged electrode
♦Lower concentration of electrons
♦Repels positively charged ions
♦Attracts negatively charged ions
♦Accumulation of negatively charged ions in a
small area creates an acidic reaction
17
18. Movement of Ions In Solution
Positively charged ions are driven into
tissues from positive pole
Negatively charged ions are driven into
tissues from negative pole
Knowing correct ion polarity is essential
18
19. Movement of Ions In Tissue
Force which acts to move ions through the
tissues is determined by
♦Strength of the electrical field
♦Electrical impedance of tissues to current flow
19
20. Movement of Ions In Tissue
Strength of the electrical field is determined
by the current density
♦Difference in current density between the active
(Active electrode- the one being used to drive the
ion into the tissue)and inactive electrodes
establishes a gradient of potential difference
which produces ion migration within the electrical
field.
20
21. Movement of Ions In Tissue
Current density may be altered by
♦Increasing or decreasing current intensity
♦Changing the size of the electrode
Increasing the size of the electrode will decrease
current density under that electrode.
21
22. Movement of Ions In Tissue
Current density should be reduced at the
cathode (negative electrode)
Alkaline reaction (+ions) is more likely to produce
tissue damage than acidic reaction(- ions)
Thus negative electrode should be larger (2x) to
reduce current density.
22
23. 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 and act to
decrease impedance facilitating the flow of
direct current as well as ions
23
24. Movement of Ions In Tissue
The quantity of ions transferred into the
tissues through iontophoresis is directly
proportional to
♦Current density at the active electrode
♦Duration of the current flow
♦Concentration of ions in solution
24
25. Movement of Ions In Tissue
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
25
26. ELECTROCHEMISTRY OF IONTOPHORETIC CIRCUIT
[ ELECTROREPULSION ]
v
Anode + Cathode -
Drug + Neutral Drug –
Na + drug Cl -
Neutral
Analyte – analyte Analyte +
Cl - Na +
BLOOD VESSEL
The number of electrons flowing through the external circuit is a direct reflection of the
amount of ionic charges flowing through the skin.
The transport number and the intensity of current are the two main parameters
controlling the iontophoretic flux.
26
27. Factors affecting iontophoresis
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 and Molecular weight
Charge
Polarity
III. Experimental conditions:
Current density
Current profile
Duration of treatment
Electrode material
Polarity of electrodes
27
28. Biological Factors:-
Intra and inter subject variability
Regional blood flow
Skin pH
Condition of skin
28
30. Iontophoresis
Generator
♦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
30
33. Current Intensity
Increase intensity slowly until patient
reports tingling or prickly sensation.
If pain or a burning sensation occur
intensity is too great and should be
decreased.
When terminating treatment intensity
should be slowly decreased to zero before
electrodes are disconnected.
33
34. Current Intensity
Maximum current intensity should be
determined by size of the active electrode.
Current amplitude usually set so that
current density falls between 0.1-0.5
mA/cm2 of the active electrode surface.
34
35. 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.
35
36. 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.
36
37. Electrode Preparation
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.
37
40. Electrode
Preparation
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
40
41. Electrode Placement
Size and shape of
electrodes can cause
variation in current
density (smaller =
higher density)
Electrodes should be
separated by at least the
diameter of active
electrode
♦ Wider separation
minimizes superficial
current density decreasing
chance for burns
41
42. Selecting the Appropriate Ion
Negative ions accumulating at the positive
pole or anode
♦Produce an acidic reaction through the formation
of hydrochloric acid
♦Produce softening of the tissues by decreasing
protein density-useful in treating scars or
adhesions
♦Some negative ions can also produce an
analgesic effect (salicylates)
42
43. Selecting the Appropriate Ion
Positive ions that accumulate at the
negative pole
♦Produce an alkaline reaction with the
formation of sodium hydroxide
♦Produce hardening of the tissues by increasing
protein density
43
45. Evaluation:-
In-vitro evaluation:-
In this experiment , the glassware is assembled,
sandwiching the excised skin. The drug
formulation is placed in donor reservoir and
normal saline is placed in the receptor
resevoir. The electrode are connected.
Periodically, solution is withdrawn from the
receptor reservoir and assayed for the drug.
In-vivo evaluation:-
The system is evaluated in rats for transdermal
iontophoretic delivery of vasopressin and
analogue in rats.
45
46. Treatment Precautions
Problems which might potentially arise from
treating a patient using iontophoresis may for
the most part be avoided if the athletic trainer
♦Has a good understanding of the existing condition
which is to be treated
♦Uses the most appropriate ions to accomplish the
treatment goal
♦Uses appropriate treatment parameters and
equipment set-up
46
47. Chemical Treatment Burns
Most common problem is a chemical burn which
occurs as a result of direct current itself and not
because of the ion being used
♦Continuous direct current creates migration of ions
which alters the normal pH of the skin
♦Chemical burns typically result from accumulation of
sodium hydroxide at cathode
♦Alkaline reaction causes sclerolysis of local tissues
♦Decreasing current density by increasing size of
cathode can minimize potential for chemical burn
47
48. Thermal Treatment Burns
Thermal burns may occur due to high
resistance to current flow created by poor
contact of the electrodes with the skin
♦Electrodes are not moist enough
♦Wrinkles in the gauze or paper towels
impregnated with the ionic solution
♦Space between the skin and electrode around
the perimeter of the electrode
♦Body weight resting on top of electrode
48
49. Application
Treatment of hyperhydrosis, diagnosis of
cystic fibrosis, other therapeutic uses.
Delivery of metallic and non-metallic ions.
Delivery of vasodilators.
Delivery of local anesthetics.
Delivery of steroids.
Uses of iontophoresis in neurosciences.
49
50. List of Drugs Investigated Recently for Iontophoretic Delivery
50
