Dielectric relaxation spectroscopy and some applications in the pharmaceutical sciences

With a few exceptions, dielectric relaxation spectroscopy (DRS) has been largely neglected by pharmaceutical scientists, despite the potential for this technique as a noninvasive and rapid method for the structural characterization and quality control of pharmaceutical materials. DRS determines both the magnitude and time dependency of electrical polarization (i.e. the separation of localized charge distributions) by either measuring the ability of the material to pass alternating current (frequency domain DRS) or by investigating the current that flows on application of a step voltage (time domain DRS). DRS is thus (i) sensitive to molecular mobility and structure, (ii) non-invasive, and (iii) employs only mild stresses (a weak electromagnetic field) in order to measure the sample properties. The technique covers a broad-band frequency window (from 10(-5) to 10(11) Hz) and therefore enables the investigation of a diverse range of processes, from slow and hindered macromolecular vibrations and restricted charge transfer processes (such as proton conductivity in nearly dry systems) to the relatively fast reorientations of small molecules or side chain groups. The dielectric response provides information on (i) structural characteristics of polymers, gels, proteins, and emulsions, (ii) the interfacial properties of molecular films, (iii) membrane properties, (iv) water content and states of water (and the effects of water as a plasticizer), and (v) lyophilization of biomolecules. This review article details the basis of dielectric theory and the principles of measuring dielectric properties (including a comprehensive account of measurement artifacts), and gives some applications of DRS to the pharmaceutical sciences.