Iontophoretic drug delivery systems

To date, Monteiro-Riviere and co-workers [60] have published the only studies using electron microscopy to examine the mechanism of iontophoretic transport. They applied mercuric chloride (7.4%) in vivo in pigs for 1 hr (current density 200 p,A/cm ) and subsequently exposed the biopsies to ammonium sulfide vapor to precipitate and localize the mercury, similar to earlier passive transport studies [28]. The micrographs revealed that mercuric chloride traverses intracellularly through the first few layers and intercellularly through the remainder of the stratum comeum. The authors concluded that the intercellular pathway is the predominant route for passive and iontophoretic drug delivery systems. However, it is difficult to eliminate follicular transport as a possible pathway, since only small areas can be examined at a time ( 1 mm ) and the low density of hair follicles (11/cm ) makes it difficult to study them with the electron microscope. 

Figure 1 Schematic representation of the basis of anodal and cathodal iontophoretic drug delivery systems.

In addition to solute structure, a number of factors affecting iontophoretic transport need to be gained for the development of useful optimal iontophoretic drug delivery systems. These include the behavior of solute ions in solution during iontophoresis, mechanisms of solute ion transport through the skin, the effect of different power sources, the choice of electrodes, the composition of vehicles, and the influence of other ions present in the process of drug delivery. 

Early iontophoretic drug delivery systems (IDDS) used materials that were not consumed during use. Commonly used materials included metals such as stainless steel or platinum. Although these nominally inert materials may have long use and storage lives, they also have significant shortcomings. 

Fig. 3 Exploded view of an iontophoretic drug delivery system showing major components top housing, printed circuit board assembly, a bottom housing containing reservoirs for placement of electrodes and hydrogels, and an adhesive laminate. (Diagram from International Patent Publication Number WO 96/39222.)...

Srinivasan et al. [17] have described a four-electrode potentiostat system which is suited to maintaining a constant voltage drop across a membrane in a two-chamber diffusion cell. This system was evaluated in connection with trans-dermal iontophoretic drug delivery of polypeptides. 

Fischer, G. A. (2005), Iontophoretic drug delivery using the IOMED Phoresor system, Expert Opin. Drug Deliv., 2(2), 391-403. 

The pharmaceutical industry has been aware of the advantages of iontophoretic drug delivery since the technique was first introduced in the field of pharmaceutical sciences. The probability of creating a safe, effective, and commercializable iontophoretic delivery system most likely will depend on three main issues iontophoretic device design, drug applied, and vehicle. 

Lidocaine is absorbed rapidly after parenteral administration and from the gastrointestinal and respiratory tracts. Although it is effective when used without any vasoconstrictor, epinephrine decreases the rate of absorption, such that the toxicity is decreased and the duration of action usually is prolonged. In addition to preparations for injection, an iontophoretic, needle-free drug-delivery system for a solution of lidocaine and epinephrine (lontocaine) is available. This system generally is nsed for dermal procedures and provides anesthesia to a depth of np to 10 mm. 

For other routes of delivery, the formulation considerations relating to polymers are less restrictive than for the parenteral route. Typically, for local rather than systemic activity, polymers can be used to enhance efficacy of topical drug delivery systems through solubility enhancement and or skin hydration. For transdermal delivery, polymers can have several roles, either as solubility modifiers, permeation enhancers or as aids in iontophoresis. The presence of multiple-charged species is a prerequisite for iontophoretic movement of drag molecules through the skin, so can be considered as an actuation process... 

As indicated in Fig. 1, a transdermal iontophoretic system requires that two electrode assemblies contact the patient s skin. The donor electrode (also known as the delivery or active electrode) contacts the drug reservoir. The counter electrode (also known as the return or receptor electrode) contacts the counter reservoir and completes the electrical circuit by providing a path for the current. The two reservoirs are separated from each other and contact skin over a fixed area. The electrodes apply an electric field across the skin by converting electric current supplied by the battery into ionic current moving in the skin and body. In doing so, a Faradaic reaction takes place at the electrode/ electrolyte interface. As described previously in this chapter, there is generally a linear dependence of the rate of drug delivery on this current. 

Hastings et al. [55] used this same in vitro technology to assess the enhancement delivery of dexamethasone using the Visulex iontophoretic system. The Visulex applicator and a freshly excised rabbit sclera were positioned between two halves of a side-by-side diffusion cell with the conjunctival side of the sclera facing the applicator (Figure 26.10). The donor drug solution (1 mg of dexamethasone phosphate) was present in the applicator, and diluted vitreous humor was modeled in the receptor cell. One milliampere direct current was applied for 60 min, and samples were collected during different treatment periods. It was demonstrated that the Visulex system produced a twofold increase in the amount of dexamethasone phosphate delivered after 60 min, compared with a standard iontophoretic administration (without the Visulex applicator). 

---