Iontophoresis physicochemical properties

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. 

Several of the physicochemical properties of insulin play an important role in determining its deliverability by iontophoresis. In order of importance, they are charge titration, solubility, enz5miatic susceptibility, and propensity for self-association. 

A second very important physicochemical property of insulin related to iontophoresis is its solubility. As is seen in Fig. 2, the rate of delivery is directly proportional to the molar concentration of the insulin in solution. Regular insulins that are marketed for the treatment of diabetes are available at a concentration of 100 units/ml, or 4 mg/ml. A higher molar concentration will, in principle (see Fig. 2), result in a higher flux, enabling the iontophoresis system to mn at a lower current. 

Iontophoresis by definition is the process of transport of ions into or through a tissue by the use of an applied potential difference across the tissue [52], Depending on the physicochemical characteristics of a molecular species, electrorepulsion is usually the primary mechanism of transdermal transport for ions, whereas electroosmosis and increased passive diffusion (as a result of the reduced barrier properties) are more prominent for neutral species [53]. In contrast, enhancement in flux for neutral or weakly charged species during electroporation arises predominantly from the reduced barrier properties of the membrane, whereas direct electrorepulsion is usually of secondary importance [25],... 

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