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SURAJ C.
Advanced Drug Delivery Systems Page 1 of 7
TRANSDERMAL
DRUG DELIVERY SYSTEMS (PHYSICAL PERMEATION ENHANCERS)
“A review write up on several Physical Permeation Enhancers/Techniques in TDDS”
Worked by:
NIKHIL SUTAR
Re-edited by:
Suraj Choudhary
I – M.PHARM
DEPT. OF PHARMACEUTICS.
2013-14
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Advanced Drug Delivery Systems Page 2 of 7
PHYSICAL PERMEATION ENHANCERS
1. Iontophoresis
2. Sonophoresis
3. Magnetophoresis
IONTOPHORESIS
A technique of introducing ionic medicinal compounds into the body through the skin by
applying a local electric current.
ADVANTAGES:
Virtually painless when properly applied.
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. Treatments are completed in minutes.
LIMITATIONS: An excessive current density = pain.
Burns = by electrolyte changes within the tissues.
High current density & time of application→generate extreme pH →chemical burn.
Electric shocks may cause by high current density at the skin surface.
Ionic form of drug in sufficient concentration is necessary for iontophoretic delivery.
MECHANISM OF ACTION: Electrode placement depends on the electric charge of ion(drug) to be delivered into the
tissue.
Electrical energy assists the movement of ions across stratum corneum according to the basic
electrical principle- -“like charges repel each other & opposite charges attract each other.”
Here the choice of drug is very important whether it is ionized or unionized.
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+ve ion will be delivered from +ve electrode & -ve ion will be delivered by -ve electrode.
When -vely charged drug is to be delivered it is placed under -vely charged active electrode= it is repelled, attracted towards +ve electrode placed.
Iontophoresis enhances transdermal drug delivery by 3 mechanisms:
Ion-electric field interaction provides an additional force that drives ions through the
skin.
The flow of electric current increases the permeability of the skin.
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 & is in
the same direction as the flow of counter-ions.
1. Passive Ionic Transdermal Drug Delivery System
Simple, relatively inexpensive & optimized enhancer patch system can accelerate the
delivery of larger electrically charged drugs.
Faster drug transport.
Enhanced safety.
More rapid onset of drug delivery.
2. Active Iontophoresis Transdermal Drug Delivery System
The application of external electric power source charges the drug substance; & facilitates
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movement of charged drugs to move into the skin.
Use of unique polymers to improve contact with skin & the rate and reliability of drug
delivery.
Use of stable & safe electrode materials for iontophoretic delivery.
Streamlined product design for ease of use & improved patient compliance.
More rapid onset of drug delivery.
Potential for better control over the rate of delivery.
Minimal skin irritation and enhanced safety.
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 of relatively small molecule size
(<8000 Daltons).
Localized treatment site.
SELECTING THE APPROPRIATE ION:
1. 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 -ve ions can also produce an analgesic effect (salicylates).
2. 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.
TREATMENT PRECAUTIONS:
Patient 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.
FACTORS AFFECTING IONTOPHORETIC DELIVERY OF THE DRUG:
Operational Factors
I. Composition of formulation:
Concentration of drug solution
pH of donor solution
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Ionic strength
Presence of co-ions
II. Physicochemical properties of the permeant:
Molecular size
Charge
Polarity
Molecular weight
III. Experimental conditions:
Current density
Duration of treatment
Electrode material
Polarity of electrodes
Biological Factors
Regional blood flow
Skin pH
Condition of skin
APPLICATIONS:
1. Inflammation With Constant Pain (Red, Hot, and Swollen)
Dexamethasone Sodium Phosphate 0.4% (negative polarity) delivered from the cathode
for 3 treatments per week for 2-4 weeks.
Diclofenac 5% (negative polarity) delivered from the cathode for 3 treatments per week for
2-4 weeks.
Ketoprofen 10% (negative polarity) delivered from the cathode for 3-5 treatments per
week for 2-6 weeks.
Lidocaine Hydrochloride 4% (positive polarity) delivered from the anode for 3-5
treatments per week for 2 weeks.
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SONOPHORESIS
Sonophoresis is a technique which involves the use of ultrasonic energy to enhance skin
penetration of active substances.
Cavitation principle. 20kHz to168 kHz.
Transdermal enhancement is particularly significant at low frequency regimes (20 KHz < f
<100 KHz) than when induced by high frequency ultrasound.
Ultrasound parameters = treatment duration, intensity, pulse length & frequency are all
known to affect percutaneous absorption. Frequency being the most important.
MECHANISM OF ACTION:
Ultrasound produces thermal & non-thermal effects.
Due to this → formation of defects in stratum corneum of size 20 micron.
The mechanism of transdermal skin permeation involves the disruption of the stratum
corneum lipids by the formation of gaseous cavities, thus allowing the drug to pass through
the skin.
Example:
a) Sonophoresis of hypotensive agents & papain = treatment of eye diseases.
b) Several antibiotics = tetracycline, biomycin, penicillin have been sonophoretically
administered for the therapy of skin diseases.
c) Sonoprep (Sontra medical corporation). Local anasthetic.
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MAGNETOPHORESIS
Application of a magnetic field = acts as an external driving force to enhance drug delivery
across the skin.
Induces alteration in skin's structure that contribute to ↑ permeability.
Magneto-liposomes
Case Study:
Study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery
and also assessed the feasibility of designing a magnetophoretic transdermal patch system
for the delivery of lidocaine.
In vitro drug permeation studies were carried out across the porcine epidermis at different
magnetic field strengths.
The magnetophoretic drug permeation "flux enhancement factor" was found to increase with
the applied magnetic field strength.
The mechanistic studies revealed that the magnetic field applied in this study did not
modulate permeability of the stratum corneum barrier.
The predominant mechanism responsible for magnetically mediated drug permeation
enhancement was found to be "magnetokinesis".
The octanol/water partition coefficient of drugs was also found to increase when exposed to
the magnetic field.
A reservoir type transdermal patch system with a magnetic backing was designed for in vivo
studies.
The dermal bioavailability (AUC(0-6h)) from the magnetophoretic patch system in vivo, in
rats was significantly higher than the similarly designed non-magnetic control patch.