Ion-exchange fibers and drugs: a novel device for the screening of iontophoretic systems.

The objective of this study was to theoretically model and experimentally measure the extent of drug release from ion-exchange fibers. The release was measured as a function of current density and NaCl concentration using a novel iontophoretic cell. The fibers tested contained weak carboxylate (-COOH) ion-exchange groups. The cationic model drugs tacrine and metoprolol were chosen on the basis of previous research, where tacrine had the lowest release rate and metoprolol the highest release rate. An in-house designed three compartment test cell was developed to test the suitability of drugs for iontophoretic drug delivery. In this cell, the anode and the drug containing ion-exchange fiber compartments were separated with a Nafion ion-selective membrane, while the fiber and the return electrode compartments were separated with a porous membrane. Tacrine proved to be a good drug candidate for this system as the release of the tacrine from the device was controllable with salt concentration and current density. Metoprolol release from the device was, however, not controllable.

Ion-exchange fibers and drugs: a transient study.

The objective of this study was to theoretically model and experimentally measure the kinetics and extent of drug release from different ion-exchange materials using an in-house-designed flow-cell. Ion-exchange fibers (staple fibers and fiber cloth) were compared with commercially available ion-exchange materials (resins and gels). The functional ion-exchange groups in all the materials were weak -COOH or strong -SO3H groups. The rate and extent of drug release from the fibers (staple fiber>fiber cloth) was much higher than that from the resin or the gel. An increase in the hydrophilicity of the model drugs resulted in markedly higher rates of drug release from the fibers (nadolol>metoprolol>propranolol>tacrine). Theoretical modelling of the kinetics of ion exchange provided satisfactory explanations for the experimental observations: firstly, a change in the equilibrium constant of the ion-exchange reaction depending on the drug and the ion-exchange material and, secondly, a decrease in the Peclet number (Pe) with decreasing flow-rate of the drug-releasing salt solution.

Ion-exchange fibers and drugs: an equilibrium study.

The purpose of this study was to investigate the mechanisms of drug binding into and drug release from cation-exchange fibers in vitro under equilibrium conditions. Ion-exchange groups of the fibers were weakly drug binding carboxylic acid groups (-COOH), strongly drug binding sulphonic acid groups (-SO(3)H), or combinations thereof. Parameters determining the drug absorption and drug release properties of the fibers were: (i) the lipophilicity of the drug (tacrine and propranolol are lipophilic compounds, nadolol is a relatively hydrophilic molecule), (ii) the ion-exchange capacity of the fibers, which was increased by activating the cation-exchange groups with NaOH, (iii) the ionic strength of the extracting salt (NaCl), which was studied in a range of 1.5 mM to 1.5 M, and finally (iv) the effect of divalent calcium ions (CaCl(2)) on the release of the model drugs, which was tested and compared to monovalent sodium ions (NaCl), and combinations thereof. It was found that the lipophilic drugs, tacrine and propranolol, were retained in the fibers more strongly and for longer than the more hydrophilic nadolol. The more hydrophilic nadolol was released to a greater extent from the fibers containing strong ion-exchange groups (-SO(3)H), whereas the lipophilic drugs were attached more strongly to strong ion-exchange groups and released more easily from the weak (-COOH) ion-exchange groups. The salt concentration and the choice of the salt also had an effect: at lower NaCl concentrations more drug was released as a result of the influence of both electrostatic and volume effects (equimolar drug:salt ratio). Incorporation of CaCl(2) in the bathing solution increased drug release considerably as compared to NaCl alone. The equilibrium distribution of the drug species between the fiber and external solution phases was also simulated and it was found that the theoretical modelling proposed describes adequately the basic trends of the behavior of these systems.

Controlled transdermal iontophoresis by ion-exchange fiber.

The objective of this study was to assess the transdermal delivery of drugs using iontophoresis with cation- and anion-exchange fibers as controlled drug delivery vehicles. Complexation of charged model drugs with the ion-exchange fibers was studied as a method to achieve controlled transdermal drug delivery. Drug release from the cation-exchange fiber into a physiological saline was dependent on the lipophilicity of the drug. The release rates of lipophilic tacrine and propranolol were significantly slower than that of hydrophilic nadolol. Permeation of tacrine across the skin was directly related to the iontophoretic current density and drug concentration used. Anion-exchange fiber was tested with anionic sodium salicylate. The iontophoretic flux enhancement of sodium salicylate from the fiber was substantial. As the drug has to be released from the ion-exchange fiber before permeating across the skin, a clear reduction in the drug fluxes from the cationic and anionic fibers were observed compared to the respective fluxes of the drugs in solution. Overall, the ion-exchange fibers act as a drug reservoir, controlling the release and iontophoretic transdermal delivery of the drug.