Iontophoretic flux

Passive and Iontophoretic Fluxes of Three Model Cationic Drugs across Different Skin Barriers... 

Drug [Applied Concentration] Skin Type Passive Flux (pg/h/cm2) Iontophoretic Flux (pg/h/mA)... 

Iontophoretic fluxes are significantly enhanced over, and less variable than, those achieved by passive diffusion. 

The total iontophoretic flux of a drug ion, therefore, is the combination of passive, electromigration, and electroosmotic contributions. The relative contribution of each mechanism depends on the characteristics of the permeant. For example, lithium, a small, highly... 

FIGURE 14.4 Linear dependence of ropinirole hydrochloride iontophoretic flux (mean SD, n > 5) upon the intensity of current applied. The transport number of the drug is estimated from the slope of the line. (Data from Luzardo-Alvarez, A., Delgado-Charro, M.B., and Blanco-Mendez, J., Pharm. Res., 18 (12), 1714, 2001.)... 

It should be mentioned that certain anomalous behavior has sometimes been observed. For example, a lack, or even an inverse effect, of drug concentration on the iontophoretic flux [32,33,96] has been reported for the lipophilic, cationic drugs such as propranolol and quinine [32,33], and for peptides such as nafarelin, leuprolide, calcitonin, and octreotide [34,96,114]. This phenomenon has been associated with adsorption of the drug onto the skin and a progressive leads to a reversal of its permselective properties (see Figure 14.6) [32,33,96],... 

YanOrman Huff, B., G.G. Liversidge, and G.L. Mclntire. 1995. The electrophoretic mobility of tripeptides as a function of pH and ionic strength Comparison with iontophoretic flux data. Pharm Res 12 751. 

SECM, was decreased by 8%, 23%, and 65% (from pretreated iontophoretic flux values) for 10-, 20-, and 30-minute pretreatment with SDS, respectively. It was concluded that the penetration enhancement effect of SDS alters the nonporous stmctures of the skin (i.e., keratin-filled comeocytes, intercellular lipid matrix). 

The passive flux of sodium ions was shown to be highly correlated (r = 0.98) to the inverse of the skin s impedance [16]. Note that since this impedance was measured at 0.2 Hz, it represents mainly the skin s electrical resistance. A weaker correlation was obtained for the passive flux of tritiated water [19]. This was found to be true both before and after the application of iontophoresis [16]. Since iontophoresis decreases the skin s impedance, the passive flux was greater after iontophoresis than before iontophoresis [16]. Inada et al. [27] have also demonstrated for tetraethylammonium ion and mannitol that their passive and iontophoretic fluxes are related to the reciprocal of the skin s resistance. In addition, Inada et al. [27] showed that the higher... 

Further evidence for pore transport is presented by Yoshida and Roberts [62] in terms of the temperature dependence of iontophoretic flux for solutes of differing size. They showed that the iontophoretic flux for sodium (MW = 23) and cyclosporin (MW = 1203) were relatively temperature insensitive (Fig. 3). The activation energies for iontophoretic transport are similar to activation energies observed for differences of solutes in aqueous solution and indicate that the iontophoretic transport of both solutes is through the pores [62]. 

The Nemst-Planck equation is conventionally applied to measure iontophoretic flux and arises from the theoretical development of Eq. 1 to define the flux of an ionic solute /, across a membrane (a) by simple diffusion due to the solute concentration gradient and (b) as a result of the electric potential difference across the membrane (electrochemical transport) [68-70]. 

When the contribution to iontophoretic flux due to convection is small and accumulation in the dermis occurs, Eq. 7 should be expressed as... 

The iontophoretic flux of an ion /, can also be defined in terms of the transport number of the solute, by... 

Figure 9 (A) lontophoretic flux of various cations across excised pig skin versus molecular weight. The donor concentration was 1.0 M of drug as chloride salt. (Data from Ref. 108.) Key. ( ) monovalent ions, (O) divalent ions. (B) Normalized cathodal iontophoretic flux of anionic solutes across hairless mice versus molecular weight. (Data from Ref. 109.) (C) Cathodal iontophoretic permeability coefficient of alkanoic acid across nude rat skin versus molecular weight. (From Ref. 64.) (D) Comparison of transport number and molecular weight in human epidermis.

A third model of iontophoretic flux arises from the idea of a retardation in the entry of solute ions into, and movement via, pores in the skin. Renkin [101] described a pore-restriction model for the diffusion of uncharged molecules through water-filled cylindrical pores. He suggested that diffusion would be restricted relative to the movement in aqueous solution by (a) steric hindrance inhibiting the entry of solute ions into the pore, and (b) hindrance due to frictional forces during the movement of solute ions through the pore. According to this model, Pjo , may be expressed by... 

Simple IT reactions are numerous and of great importance for biological systems (40). Unlike both ET and facilitated IT processes, no mediator species is involved in a simple IT reaction. It can be induced in two different ways either by application of external voltage across the interface or by depleting the concentration of the common ion in one of two liquid phases near the ITIES. White and coworkers used the first approach to probe localized iontophoretic fluxes of electroactive species (e.g., Fe2+) through artificial membranes and hairless mouse skin (54). The tip scanned over the membrane surface detected the species driven through pores by applied volt-... 

Transport Numbers for the Iontophoretic Flux of Various Peptides with Differing Molecular Weights through Human Skin in the Presence and Absence of an... 

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