Passive transdermal administration of drugs, as with a skin patch, is suitable for non-ionized drugs requiring a relatively small dosage. Ionized drugs, however, do not easily penetrate the skin and are therefore not generally suitable for routine transdermal dosage. An external energy source in the form of an applied direct electrical current will increase the rate of penetration by assisting the movement of ions, driving the drug across the skin. Like charges repel each other and opposite charges attract. Thus, positive ions in a water- soluble medication are repelled from a positively charged electrode positioned over the tissue into which the medication ions are to be delivered, and negative drug ions are repelled from a negatively charged electrode. The direct current moves the ions from the drug electrode through the patient’s skin. In iontophoresis, a charged molecule is delivered across the skin, by placing it near the electrode of like charge, while the electrode of opposite charge is placed elsewhere on the body. Ionophoresis

Types Anodal and cathodal iontophoresis, both consisting of a basic iontophoretic setup with a set of electrodes (anode and cathode), drug and salt reservoirs and a current source. Thus positively charged ions can be delivered by placing them under the positive electrode (anode) creating repulsion and at the same time creating an attractive force by placing the negative electrode at a distal site on the skin. At the same time, negatively charged ions from the body (primarily Cl-) move toward the anode. For cathodal iontophoresis, the electrodes are reversed so that a negatively charged drug is delivered through skin.

Pathways for Iontophoretic Transport Iontophoretic transport is said to occur primarily through the transappeandageal (shunt pathway) and the paracellular route, however the appendageal pores such as the hair follicles and the sweat glands are most efficient in iontophoresis and major transport occurs through this route. Iontophoresis can also enhance skin delivery by a potential-dependant pore formation in the stratum corneum. Drug Concentration: Increased uptake by the skin during and after IP with an increase in drug concentration has been reported. This is generally true until a plateau level is reached at which no further increase in flux is observed because of the saturation of the boundary layer. Factors influence iontophoretic transport pH : The pH of the formulation should be optimized to ensure maximum ionization of the compound. Competing Ions in the Electrodes: Electrical current is carried by positive and negative ions in solution. There is no major distinction between ions of the same charge even though they are composed of different chemical elements. Therefore, solutions for IP should be as pure as practical and generally contain as few extraneous substances as possible. Drug solutions should be prepared with purified water(deionized, distilled, reverse osmosis).

Molecular size: When the molecular size increase the permeability coefficient decreases for positively and negatively charged solutes, However, there are certain solutes with a relatively high molecular size (insulin & growth hormone) can penetrate the skin barrier into the systemic circulation. Physiological factors: There are small differences in the flux rate following transdermal iontophoresis between males and females as well as hairy and hairless skin. The status of the vascular bed is also important, a pre-constricted vascular bed decreases the drug flux while a dilated vascular bed increases the yield of the drug through the skin. Current density: Current density is the quantity of current delivered per unit surface area. The following criteria should be considered in selecting proper current densities for IP: (1) the current should be sufficiently high to provide a desired drug delivery rate; (2) it should not produce harmful effects to the skin; (3) there should be a quantitative relationship between the flux and the applied current; and (4) there should be electrochemical stability of the drug.

Microneedle Patches The microneedle patch has an array of microscopic needles (each is about 150 micron). The needles can be fabricated to be long enough to penetrate the stratum corneum, but short enough to not come into contact with nerve endings. Microneedle patches are currently being explored as mechanisms to deliver vaccines and larger macromolecules. The microneedles can be made from a harmless dissolving polymer that's mixed with a freeze-dried vaccine. So instead of the needles injecting a fluid, the needles quickly dissolve to become the fluid. When the patch is pulled off, there's nothing sharp left on it,