A series of glyceryl monoolein/water liquid crystal systems containing 15%, 20%, 30%, and 35% w/w water have been investigated using dielectric spectroscopy over a frequency range of 10 -3 -10 6 Hz and a temperature range of 20-90 °C in order to facilitate association of the lyotropic and thermotropic phase behavior with the dielectric response. The phase boundaries of the mixes were determined independently using hot stage microscopy. The frequency-dependent dielectric spectra of systems containing lamellar, cubic, and hexagonal phases are reported and have been modeled using circuits corresponding to generalized Maxwell-Wagner responses. More specifically, the systems were found to correspond to a parallel bulk capacitance and conductance in series with a Maxwell-Wagner blocking capacitance, which was associated with an adsorbed layer at the electrode surfaces. An additional dispersion was observed corresponding to a series RC circuit, which was associated with charge transport across the lipid bilayers. It is proposed that the dielectric responses of the lamellar, cubic, and hexagonal phases exhibited by these systems may be described in terms of equivalent circuit models, which may in turn be related to specific structural features of the sample.

The objective of the study was to investigate the use of low frequency dielectric spectroscopy as a means of characterizing the thermal transitions of an amorphous drug substance, indometacin, with particular emphasis on modelling the response using the Dissado-Hill function. The low frequency dielectric behaviour of indometacin was measured over a temperature range of 10-160 degrees C and a frequency range of 10(-3)-10(6) Hz. Modulated temperature differential scanning calorimetry (MTDSC) studies were also performed on equivalent samples, showing a glass transition, recrystallization and melting. Isothermal low frequency dielectric spectra of the sample at temperatures below recrystallization showed the dynamic dielectric relaxation associated with the amorphous phase, while changes in the real and imaginary permittivities were observed that were associated with recrystallization and subsequent melting. A small discontinuity was observed immediately above the recrystallization process in the MTDSC and dielectric data, suggested to correspond to a solid state transformation. The use of the Dissado-Hill function as a means of modelling the dielectric behaviour has also been described. The study suggests that low frequency dielectric spectroscopy, used in conjunction with MTDSC and Dissado-Hill modelling, may be a useful tool for the characterization of amorphous and crystalline drugs.

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The influence of propantheline bromide incorporation on the phase structure of glyceryl monoolein/water systems has been investigated using low-frequency dielectric spectroscopy over a frequency range of 10(-2) to 10(6) Hz at 20 degrees C. The responses of glyceryl monoolein systems composed of 10% and 30% w/w were measured and the spectra modeled using an equivalent circuit based on the Maxwell-Wagner theory.1,2 Marked changes in the dielectric responses of the systems were noted on addition of the propantheline bromide at concentrations up to 10% w/w. For the lamellar (10% w/w water) glyceryl monoolein systems, an increase in the imaginary permitivity was seen, corresponding to an increase in conductivity due to the presence of additional ionic species within the system. Evidence was also obtained for the incorporation of the drug directly into the lipid bilayers, particularly at higher concentrations (10% drug) at which dielectric behavior corresponding to bilayer disruption was seen. Incorporation of 3% and 5% w/w drug into the cubic phase systems (30% w/w water) resulted in a change to the lamellar phase. However, circuit modeling indicated that the system formed structures which showed features of both the lamellar and cubic phases at 3% w/w drug loadings. The study has therefore demonstrated that dielectric analysis may provide a novel means of studying the effects of drug incorporation on the phase behavior of complex gel systems.

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