Dielectric properties of sucrose solutions: role of free water and hydration dynamics in microwave-assisted freeze-drying (MAFD) at 2.45 GHz

Microwave assisted freeze drying of pharmaceuticals has the potential to significantly reduce the drying time. Microwave radiation directly penetrates the formulation resulting in volumetric heating which is dependent on the dielectric loss factor of the formulation. The purpose of this work was to identify the primary source of microwave heating in solutions of sucrose, a common lyoprotectant, by measuring the dielectric loss factor of sucrose solutions (5%–72% w/w) at temperatures relevant to freeze-drying (-40 to 20 °C) process using a short circuit line method from 0.9 to 6 GHz. The loss factor generally decreased with temperature and frequency. Solutions with ice (5–50% w/w) showed significantly lower loss factor as compared to formulations without ice (60–72% w/w), even at comparable temperatures. The loss factor of solutions with ice (5–50% w/w) increased with concentration whereas that in solutions without ice (60–72% w/w) decreased. Additionally, correlations of loss factor with volume fractions of freeze concentrate, unfrozen water and free water were evaluated. Sucrose hydration models were adapted to determine the free water fractions in frozen aqueous sucrose. A good correlation of loss factor with free water suggests that free water fraction is primarily responsible for microwave heating. A secondary viscosity effect was identified. The results can be used in estimating the volumetric heating of sucrose-based formulations by microwave energy in microwave assisted freeze-drying (MAFD) of pharmaceuticals at 2.45 GHz and can be further extended to sucrose-dominated formulations. The improved estimates for loss factor of sucrose solutions can be used for improving model-based optimization of microwave-assisted freeze drying of pharmaceuticals.