Transdermal Drug Delivery Systems - (Physical enhancers through the skin) - A writeup (its the remaining part of already uploaded part earlier)

1. SURAJ C.
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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

2. SURAJ C.
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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.