Dielectric properties of residual water in amorphous lyophilized mixtures of sugar and drug

Abstract

Dielectric relaxation spectroscopy was used to investigate the properties of residual water in lyophilized formulations of a proprietary tri-phosphate drug containing a sugar (trehalose, lactose or sucrose) or dextran. The dielectric properties of each formulation were determined in the frequency range (0.1 Hz-0.1 MHz) and temperature range (30˚C-T g ). The temperature dependence of the relaxation times for all samples showed Arrhenuis behaviour, from which the activation energy was derived. Proton hopping through the hydrogen-bonded network (clusters) of water molecules was suggested as the principle mode of charge transport. Significant differences in dielectric relaxation kinetics and activation energy were observed for the different formulations, which were found to correlate with the amount of monophosphate degradation product.

Coupling of dielectric and mechanical relaxations with glass transition and stickiness of milk solids

“…Relaxation times are extremely long in the glassy state but a dramatic decrease in relaxation times occurs above the T g (Williams et al, 1955;Angell et al, 1982;Moynihan, 1993;Perez, 1994;Roos, 1995;Slade and Levine, 1995;Angell, 2002;El Moznine et al, 2003). In our previous study, we found a strong link between the glass transition, a-relaxations and flow characteristics of milk solids (Silalai and Roos, 2010a).…”

“…The temperature dependence of the a-relaxation time (s a ) was modeled using the Vogel-Tamman-Fulcher (VTF) relationship of Eq. (1) (Chan et al, 1986;Angell et al, 1982;El Moznine et al, 2003;Angell, 2008).…”

Local Mobility in Amorphous Pharmaceuticals—Characterization and Implications on Stability

“…Interestingly, the temperature of secondary relaxations was found to increase when sucrose was also present in the starch-water matrix indicating the importance of specific interactions in determining the effect on local motions. Moznine et al 80 studied the effect of the interaction of residual water with lyophilized sugars. They observed that the faster noncooperative dielectric relaxations, resulting from a protonic charge transfer process in presence of water, determined the degradation rates of the sugars.…”

Mechanical relaxation times as indicators of stickiness in skim milk–maltodextrin solids systems

“…The temperature dependence of the a-relaxation time (s a ) was modeled using the Vogel-Tamman-Fulcher (VTF) relationship of Eq. (1) (Angell et al, 1982;Chan et al, 1986;El Moznine et al, 2003;Angell, 2008).…”