Percolation phenomena in controlled drug release matrices studied by dielectric spectroscopy and the alternating ionic current method

Abstract

The combined radial and axial ionic drug release from – as well as the percolating ionic conductivity in – cylindrical tablets was investigated by the alternating ionic current (AIC) method and dielectric spectroscopy (DS), respectively. The binary tablets consisted of mixtures of insulating ethyl cellulose and the poor ionic conductor model drug NaCl at nine different concentrations. We found that the dc conductivity, extracted from DS in a well-defined range of frequencies by a power-law method, could be described by a NaCl volume fraction percolation threshold of ∼0.06 in a 3D conducting network. The low threshold was explained by water-layer-assisted ion conduction in μm-sized ethyl cellulose channels between NaCl grains as probed by Hg porosimetry and SEM. The drug release process, as probed by AIC, could be described by a matrix porosity percolation threshold of 0.22, equivalent to a NaCl volume fraction of ∼0.13. The higher percolation threshold found in the drug release experiments as compared to the DS recordings could be explained by the different probing mechanisms of the analysis methods. The present study should provide valuable knowledge for the analysis of a broad class of ion conducting systems for which the frequency response of the dc ion conductivity is superimposed on other dielectric processes in the dielectric spectrum. It also brings forward knowledge important for the development of controlled drug-delivery vehicles as the presented findings show that the drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces.