An investigation into the thermal behaviour of an amorphous drug using low frequency dielectric spectroscopy and modulated temperature differential scanning calorimetry

Abstract

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.

Different Measures of Molecular Mobility: Comparison between Calorimetric and Thermally Stimulated Current Relaxation Times Below Tg and Correlation with Dielectric Relaxation Times Above Tg

“…Relaxation times were calculated using the VTF equation (experimental input parameters, generally the configurational entropy and fragility (m) are estimated quickly using DSC) 10. Different experimental techniques have previously been used to measure molecular mobility in the glassy state such as enthalpic recovery experiments in the DSC,11–14 isothermal microcalorimetry (TAM),14–16 thermally stimulated depolarization current spectroscopy (TSDC),17, 18 dielectric relaxation,19–21 nuclear magnetic resonance,22 and viscosity measurements 23, 24…”

The Slow Molecular Mobility in Amorphous Ketoprofen and Ibuprofen

“…On the contrary, a discrepancy is sometimes observed comparing m values obtained by different experimental techniques. An example is indomethacin, where values near m = 60 are obtained by TSDC and by DSC, whereas m = 81 is obtained from dielectric relaxation data . This may arise from the different nature of the experimental probes used (viscosity, dielectric, mechanical, enthalpy relaxation, …).…”

Sulfoalkyl ether β-cyclodextrin derivatives synthesized by a single step method as pharmaceutical biomaterials

“…All samples were placed in a sealed aluminum pan and heated from 10 to 400℃ at a rate of 10℃/min and under a nitrogen flow of 20 cm 3 /min. An empty pan sealed and heated in the same way was used as reference [34,35] .…”