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Iontophoresis cathodal

Figure 8. Transdermal flux of monomeric insulins during in vitro iontophoresis (cathodal... Figure 8. Transdermal flux of monomeric insulins during in vitro iontophoresis (cathodal...
Electrically assisted transdermal dmg deflvery, ie, electrotransport or iontophoresis, involves the three key transport processes of passive diffusion, electromigration, and electro osmosis. In passive diffusion, which plays a relatively small role in the transport of ionic compounds, the permeation rate of a compound is deterrnined by its diffusion coefficient and the concentration gradient. Electromigration is the transport of electrically charged ions in an electrical field, that is, the movement of anions and cations toward the anode and cathode, respectively. Electro osmosis is the volume flow of solvent through an electrically charged membrane or tissue in the presence of an appHed electrical field. As the solvent moves, it carries dissolved solutes. [Pg.145]

The previous model [57] has been further developed for the iontophoretic delivery of a monovalent drug. The first case considered (the single-ion situation) is exemplified by the anodal iontophoresis of a monovalent, cationic drug (m+), which is the only available charge carrier at the skin surface. The cathodal (subdermal) electrolyte is assumed to be normal saline. Under these circumstances, the transport number of the drug is given by... [Pg.286]

In summary, there is evidence that the skin presents a weak cation permselectivity [25,76,77,80,93,125], which can be reversed by acidifying the pH of the solutions bathing the skin [10,23,76,77]. At pH>p/, the skin is negatively charged and electroosmotic flow proceeds in the anode-to-cathode direction. At pH < pi, the skin becomes positively charged and electroosmotic flow reverses to the cathode-to-anode direction. Under the application of an electric field, counterions (cations at physiological pH) are preferentially admitted into the skin. As a consequence, the sodium and chloride transport numbers are 0.6 and 0.4, respectively, during transdermal iontophoresis (in contrast to their values in a neutral membrane tNa = 0.45 rCi = 0.55) [126]. [Pg.296]

Current was delivered to the membranes through silver/silver chloride (Ag/AgCl) electrodes for iontophoresis, whereas stainless steel electrodes were employed for electroporation studies. Of the two model compounds, L-glutamic acid carries a net negative charge of 1 at pH 7.4, whereas estradiol is nonionized. Hence, they were delivered under the cathode and anode, respectively. [Pg.306]

Figure 11 lontophoretic permeability coefficient (PCjont.) of various negatively charged solutes in cathodal iontophoresis at 0.38 mA/cm. (A) log PCiont. versus log MV. (B) log PCiont. versus MV. (C) log PC,ont. versus radius. (Redrawn from Ref. 62.)... [Pg.322]

Fig. 3 Schematic representation of iontophoresis. Two electrode chambers, connected to a power source, are placed in contact with the skin. Upon application of the electric field, drug ions are repelled from the electrode of similar polarity (in this case, cations are repelled from the anode). This electrorepulsion (ER) also imposes inward motion on i) other cations present in the anode formulation, and ii) the outward transport of anions (e.g., CP) from within the skin. At the non-working electrode (in this case, the cathode), negative anions from the electrolyte are driven into and through the skin, while cations (e.g., Na ) are extracted from the tissue. The direction of the electroosmotic flow (EO) is also shown. Fig. 3 Schematic representation of iontophoresis. Two electrode chambers, connected to a power source, are placed in contact with the skin. Upon application of the electric field, drug ions are repelled from the electrode of similar polarity (in this case, cations are repelled from the anode). This electrorepulsion (ER) also imposes inward motion on i) other cations present in the anode formulation, and ii) the outward transport of anions (e.g., CP) from within the skin. At the non-working electrode (in this case, the cathode), negative anions from the electrolyte are driven into and through the skin, while cations (e.g., Na ) are extracted from the tissue. The direction of the electroosmotic flow (EO) is also shown.
Fig. 4 Imposing an electrical potential gradient across a charged membrane produces a convective solvent flow in the direction of counter-ion transport (i.e., from anode-to-cathode in the case of skin). This electroosmotic effect (EO) adds to electrorepulsion (ER) to enhance the transport of cationic compounds during iontophoresis (4a) while acting against the electromigration of anions (4b). Fig. 4 Imposing an electrical potential gradient across a charged membrane produces a convective solvent flow in the direction of counter-ion transport (i.e., from anode-to-cathode in the case of skin). This electroosmotic effect (EO) adds to electrorepulsion (ER) to enhance the transport of cationic compounds during iontophoresis (4a) while acting against the electromigration of anions (4b).
A method to force C. roseus cells to excrete the produced alkaloids into the medium by iontophoresis is described by Pu et al. (629). The authors demonstrated that a direct current of 1-2 mA was sufficient to enable the release of the alkaloids ajmalicine and yohimbine. The reactor used consisted of a single porous hydrophilic ceramic tube with a pore size of 0.2 nm housed in a 11-cm-long glass tube 1.6 cm in internal diameter. Two platinum wires were used as electrodes, with one placed evenly in the shell region of the reactor as anode and the other placed in the ceramic tube as cathode. It was shown that the application of a direct current caused a release of ajmalicine of approximately 0.4 mg/liter/hr per gram dry cell mass. Passive diffusion of alkaloids from the cells was negligible. The increase of the direct current from 1 to 2 mA effectively doubled the release of ajmalicine. [Pg.136]

Panus, P.C. Ferslew, K.E. Tober-Meyer, B. Kao, R.L. Ketoprofen tissue permeation in swine following cathodic iontophoresis. Phys. Ther. 1999, 79 (1), 40-49. [Pg.108]

The authors then tried cathodal iontophoresis of a monomeric form of insulin, sulfated insulin, in pigs in the belief that the smaller molecular size of the monomeric insulin (MW 5800) versus hexameric regular insulin (MW 35,000) would iontophorese better. In one of the animals studied, a large rise in serum insulin which correlated with a large fall in serum glucose was observed. However, in each of the other animals studied, no similar result was obtained. The authors concluded that insulin iontophoresis is possible and that a smaller monomeric insulin is important. The reasons for failure in all the animals but one remain unknown. [Pg.331]

Meyer et al. (1989) also studied iontophoresis of regular insulin in alloxanized rabbits. Cathodal iontophoresis was used as in the work of Kari (1986), but the skin was not abraded. In order to reduce the average molecular weight of the insulin, urea was added to the formulation. While a significant increase in serum insulin and decrease in serum glucose were recorded on average versus controls (4 control animals, 15 treated animals), there were some animals that did not respond to the treatment. [Pg.331]

An iontophoretic dosage form for the delivery of insulin would be of little benefit if diabetics could not wear it. Recently, the skin response to a 24-hr iontophoresis dosage form was measured in human volunteers (Maibach, 1994). In terms of comparisons of iontophoretic patches at 200 /A/cm2 and similar patches without current, no significant changes were measured for transepithelial water loss (TEWL), skin capacitance, and skin temperature. The only effect was modest transient erythema. For a 24-hr application, this establishes a well-tolerated current density. In order to determine a well-tolerated total current, we need only know the skin contact area. Experience with passive patches has shown that a total area of SOcm for a system worn all day, every day, may be close to a maximum. Allowing 20 cm2 for si-in adhesion and 30 cm for the anode and cathode, a IS-cm electrode area is estimated. For a current density of 20Q A/cm2, this yields an estimate of 3 mA as well tolerated for a system worn aU day, every day. [Pg.333]

Of the published data on in vivo iontophoresis of insulin, perhaps the most interesting are those obtained in pig studies with sulfated insulin (Stephen et al, 1984) since pig skin is very similar to human skin. Sulfated insulin has an isoelectric point of about pH 2, which would give it a strong negative charge at all pHs encountered in skin. Such an insulin should be deliverable by cathodal iontophoresis. A large dose was delivered in one pig. It remains a mystery why a similar dose delivery was not seen in any of the other pigs. [Pg.337]


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