Percolation phenomena in controlled drug release matrices studied by dielectric spectroscopy and the alternating ionic current method U. Brohede, M. Strømme * Department of Engineering Sciences, The A ˚ ngstro ¨ m Laboratory, Uppsala University, P.O. Box 534, SE-751 21 Uppsala, Sweden Available online 25 September 2007 Abstract The combined radial and axial ionic drug release from – as well as the percolating ionic conductivity in – cylindrical tablets was inves- tigated by the alternating ionic current (AIC) method and dielectric spectroscopy (DS), respectively. The binary tablets consisted of mix- tures 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 con- duction in lm-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. Ó 2007 Elsevier B.V. All rights reserved. PACS: 81.05.Rm; 77.84.Lf; 77.22.d Keywords: Biopolymers; Pharmaceuticals; Conductivity; Dielectric properties, relaxation, electric modulus; Porosity 1. Introduction Binary systems consisting of an insulating matrix with an ion conducting material incorporated are important for several research and application areas within, e.g., poly- mer technology, geology, electrochemistry and pharmaceu- tics. For such systems the percolation threshold, signifying the conducting component volume fraction at which ion conducting channels spans the entire matrix, in many aspects determines the functionality of the system [1–7]. In spite of this, percolation studies in the literature analyzing binary mixtures of conducting and non-conduct- ing materials hitherto have focused almost entirely on mix- tures containing electron – and not ion – conductors [8–12]. One exception to this is within the pharmaceutical sciences where a few studies have been presented involving release of an ion conducting material or of a material that ionizes when in contact with a liquid in order to assess the perco- lation threshold of the mixture [7,13]. In these pharmaceutical studies, percolation theory (PT) has been used to describe one-dimensional drug release from matrix systems. Experimentally, this was accom- plished by covering all matrix surfaces except a planar one by paraffin [13,14]. From a theoretical point of view, the assumptions of a three-dimensional structure and one-dimensional drug release are convenient. In practice, 0022-3093/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jnoncrysol.2007.02.081 * Corresponding author. Tel.: +46 18 471 7231. E-mail address: maria.stromme@angstrom.uu.se (M. Strømme). www.elsevier.com/locate/jnoncrysol Available online at www.sciencedirect.com Journal of Non-Crystalline Solids 353 (2007) 4506–4514