Electrical field. The net charge on skin

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based permeation enhancement


Iontophoresis/ionization is technique of
delivering drug ions diffused in a medium driven by electric current (Fig). During iontophoresis uncharged solvent molecules are also
carried with charged ions due to the process of electro osmosis. It employs an
electromotive drug administration device which drives the medicine in ionic
form through the skin surface.  The
charged drug is delivered transdermally by the repulsive electromotive force.
The device has two chamber, one or two filled with drug ions and solvent
vehicle. One chamber containing positively charged ions is called the anode,
while negatively charged chamber is called cathode.  A small electric current is applied to the
device chambers positioned on the skin. The anode will repel positively charged
ions, while cathode will do the reverse and force negatively charged species
into the skin. The drug delivery can be controlled in such iontophoretic
devices by the mean magnitude of current (i.e. the charge generated in circuit)
which determine the number of ion species fluxed across the skin.

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However several factors affect the efficiency of iontophoretic
system e.g.

1) Drug concentration

is established that generally drug concentration and iontophoretic flux show
linear relationship, however when the concentration of the drug
is exceeded beyond flux plateaus, it does not increase the flux any further or reduce. This happens due to
charge saturation of aqueous conducting channel of skin and concentration of
competing ions also play significant role.  In cases where there are no competing ions,
the iontophoretuic flux is shown to be independent of drug concentration, e.g.
lidocaine hydrochloride and R- apomorphine hydrochloride.



2) pH of the formulation-Generally skin carries net negative
charge at physiological pH and hence it is permselective
to positively charged drug molecules under the influence an electrical field.
The net charge on skin can be modified through change in pH of the drug
formulation which can manoeuvre the electroosmotic and electrorepulsive forces
balance in iontophoretic transport 44–46.The drugs ionization state can be
changed by changing pH of the formulations which will cause modification in its
electrophoretic mobility e.g. a weakly basic drug at pH higher than its pKa
value is ionized to a lower extent and will not infuse in the skin . So the pH of the formulation is crucial for successful
transdermal drug delivery.


Electrolyte: An Iontophoretic device generally uses electrolytes for
electrochemical functioning of the device. However electrolyte component ion
Na+ and Cl- are themselves very efficient charge carriers compete with drug
ions and preferentially transported across the skin, hence they should be
avoided if possible 47.


than drug delivery, in some biosensing devices the reverse iontophoresis is
employed where it removes some molecules from within the body and detected. At
buffered pH, the skin carries a net negative charge and become permiselective
to Na+ and K+ cations, which causes the movement of solvent towards anode by
the process of electroosmosis. This electro- osmosis then leads to
electrophoresis of glucose across the skin, and this is then detected by
glucometer of Glucowatch. Similarly pliocarpine
cutaneous iontophoresis is used as diagnostic test hypohidrosis in ectodermal dysplasia and for cystic fibrosis, 
where stimulation of sweat secretion takes place due to the drug and
further the chloride levels in sweat is assayed. In 2004 FDA has
approved a lidocaine–epinephrine iontophoretic
system under the name LidositeTM patch which is used to induce local
anaesthesia in rapid and effective manner in paediatric patients. The system is
consist of three different components a) 
iontophoretic current generating device (Phoresor ®)) 2% lidocaine HCl
with1:100,000 epinephrine solution (Iontocaine®) and c) hydrogel electrodes
(Numby Stuff™).  Epinepharine is vasoconstrictor which
prolongs the duration of lidocaine action at the site by delaying resorption as
well as force the drug to pass
further than the capillaries and be delivered to the deeper tissues.

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