Quantitative structure–permeation relationship for iontophoretic transport across the skin

Abstract

The objective was to relate the efficiency of a charged drug to carry current across the skin during iontophoresis to its structural and/or physicochemical properties. The corollary was the establishment of a predictive relationship useful to predict the feasibility of iontophoretic drug delivery, and for the selection and optimization of drug candidates for this route of administration. A dataset of 16 cations, for which iontophoretic fluxes have been measured under identical conditions, with no competition from exogenous co-ions, was compiled. Maximum transport numbers correlated with ion mobilities and decreased with ionic size, the dependence indicating that the electromigration mechanism of iontophoresis would become negligible for drugs of hydrodynamic radius greater than about 8 A. Validation of the model was demonstrated by successfully predicting the transport numbers of three structurally distinct dipeptides, the iontophoretic data for which had been determined under distinctly different experimental conditions. Finally, for the "training" set of cations, a strong linear dependence between their transport numbers in skin and those in aqueous solution was demonstrated; the former were larger by approximately a factor of 1.4 consistent with skin's cation permselectivity. In conclusion, this research offers a practical contribution to the development of a predictive structure-transport model of iontophoresis.

Cutaneous Microdialysis

“…The transport number of the ion of interest. Transport numbers are difficult to predict but it is known that in the presence of competing ions, as is the case of reverse iontophoresis, the transport number of an ion will be directly proportional to its concentration in the subdermal fluid and to its electrical mobility [19,[23][24][25][26][27]. Obviously, the ions that are more mobile and present in high concentrations, will play the main role in the movement of charge through the skin.…”

“…Thus, reverse iontophoresis provides measurements of free drug concentration, an interesting feature for some drugs ( Figure 6.2). Finally, the ionic mobility (which contributes to the value of the transport number) is inversely related to molecular size [23]. In summary, the best candidates to be extracted by reverse iontophoresis (by electromigration) are small, fully charged, highly concentrated, and not significantly protein-bound compounds; an excellent case has been that of lithium, for example.…”

Quantitative analysis of iontophoretic drug delivery from micropipettes

“…Although this is the more complete term, distinction between transference and transport numbers is rarely reflected in current literature. 27, 28 …”

Effective use of transdermal drug delivery in children

“…An optimized formulation (10% lidocaine and 0.1% epinephrine) was used and provided anaesthesia in only 10 minutes; systemic exposure to lidocaine was very low with 11 out of 12 subjects showing concentrations below the LoD (5 ng.mL -1 ), and the other slightly more (8.9 ng.mL mL -1 ) [164]. Quite likely, the increased content of lidocaine (compared to previous formulations) resulted in a larger drug transport number (and iontophoretic flux) [165]. The reduced epinephrine content was selected to achieve a degree of vasoconstriction so that the local anaesthetic residence time was adjusted appropriately without compromising the venipuncture procedure.…”