Iontophoresis theoretical models

Pikal, M.J. 1990. Transport mechanisms in iontophoresis. I. A theoretical model for the effect of electroosmotic flow on flux enhancement in transdermal iontophoresis. Pharm Res 1 (2) 118. 

Ocular iontophoresis has been very poorly evaluated with in vitro models, in comparison to the work that has been done in the transdermal iontophoretic field. This general lack of a strong theoretical foundation for the practice of ocular iontophoresis has led to many useless animal experiments with no beneficial results due to drug or current unsuitability. Most of the preliminary experiments for optimization of the iontophoretic system were performed on animals. 

The graph in Fig. 2 can be used to address the most fundamental question regarding insulin iontophoresis—is it theoretically possible, under the most favorable conditions, to deliver the required dose Based on the discussion in Section 2.1, the needs are a basal delivery rate of 1-2 units per hour coupled with a bolus of up to 20 units over about a half-hour. Figure 2 indicates that a delivery rate of 40 units per hour could be achieved with a 1 mM solution of insulin, which is equivalent to about 4mg/ml or 100 units/ml. Regular (currently marketed human, pork, or beef) insulin has a water solubility that exceeds this value. Thus, it is theoretically possible to iontophorese insulin at the required rate. However, an idealized model has been used to reach this conclusion. Specifically, it was assumed that insulin exists as an ideal solution (with a MW of 5800), that the mobility of insulin is independent of pH and has a value close to its maximum value, and that the molecule is not degraded on its way through the skin. For regular insulins, these assumptions are not true. In the next section, the physicochemical properties of insulin that impact its deliverability by iontophoresis are described. 

---