Pulsatile release of an ionizable drug from microcapsules with electrochemomechanical walls

An electric field has been used to alter and control the release of an ionizable compound from microcapsules with electrochemomechanical (ECM) walls. The electric current was applied to the system to cause changes in pH which affects not only the solubility and charge of the drug, but the physical properties of the gel wall matrix as well. In this manner, by simply altering the electric current in on/off cycles, in vitro electrically-facilitated drug release in controlled pulsatile patterns can be achieved. The system consisted of four components: an ionizable drug core, an electrochemomechanical hydrogel wall, an aqueous electrolytic suspension medium, and an external power supply. Sulfadiazine is an ionizable drug and was used as the model compound for these studies. Gelatin, Type B, was the model ECM hydrogel wall.; The experimental protocol first involves microencapsulation of drug with an ECM hydrogel. In vitro drug release from microcapsules has been carried out under passive conditions and under the influence of an electric current. In most cases, platinum wire electrodes were used for the electrically-facilitated release studies. Currents of 0, 0.5, and 1.0 mA DC were applied to microcapsules from t = 20 to t = 50 min. Sulfadiazine release was dependent on the magnitude of the applied current in that there were 5.20 and 11.0 fold increases in the amounts of sulfadiazine released after 70 min compared to that by passive diffusion. In order to test the effect of pH on sulfadiazine release, passive and electrically-facilitated release studies were carried out using sulfadiazine suspensions, suspensions of gelatin/sulfadiazine microcapsules and suspensions of PVP/sulfadiazine microcapsules using four different pH protocols. It was determined that the electrically-facilitated release of sulfadiazine can occur by one or a combination of the following mechanisms: (1) passive diffusion through the microcapsule hydrogel wall, (2) diffusion through pores in the wall created by or closed by the electrically induced pH change in the donor compartment, (3) an increase in the solubility of sulfadiazine in the donor compartment caused by pH fluctuations induced by the reactions at the electrodes, (4) iontophoresis of charged drug through the microcapsule hydrogel wall and/or SpectraPor ® membrane, and (5) solvent flow or electroosmosis of drug solution through the wall. (Abstract shortened by UMI.)...