Abstract
In the production of several anticancer drugs, tert-butyl alcohol (TBA) is present as a co-solvent in the aqueous drug solution. In order to ascertain if TBA should be removed beforehand or if it could be retained to facilitate the freeze-drying of the drug solution, it is important to acquire both qualitative and quantitative knowledge of the variations occurring with respect to time in heat and mass transfer during the freeze-drying process. In this work, a thermodynamic model employing the UNIFAC (Dortmund) method was developed to determine the values of the currently experimentally unavailable partial vapor pressures of the binary gas mixture of water and TBA in equilibrium with their frozen solid mixtures. The results agree satisfactorily with relevant experimental measurements and indicate that TBA vapor has constantly higher pressures than water vapor and also promotes the vapor pressure of water during sublimation. The responses of the partial pressures of water and TBA vapors are found, through the analysis of their partial and total differentials, to be increasingly more sensitive to temperature change at elevated temperatures and to compositional change when the mole fraction of water in a frozen binary mixture approaches zero. The increased vapor pressures due to TBA lead to higher total pressures at the moving interface separating the dried and frozen layers, resulting in larger total pressure gradients and convective mass transfer rates in the dried layer during primary drying. But the higher total pressures reduce the magnitude of the bulk diffusivity of the gas mixture, and combined with the smaller Knudsen diffusivity of TBA, the pressures could significantly affect the competing mass transfer mechanisms during freeze-drying. The approach presented in this work could provide a general thermodynamic modeling approach for predicting the vapor pressures of multicomponent vapor mixtures in equilibrium with their multicomponent solid frozen mixtures.
LAY ABSTRACT: tert-Butyl alcohol (TBA) is present as a cosolvent in a number of anticancer drug solutions. Its presence is known to affect the freeze-drying process of the drug solutions. In order to determine a better operational policy with respect to the freeze-drying process, a thermodynamic approach was developed in this work to provide the needed data of water and TBA vapors that are currently experimentally unavailable. The results agree satisfactorily with experimental measurements. They indicate that TBA vapor has constantly higher pressures than water vapor, promoting faster sublimation and generating higher total pressures at the moving interface to enhance convective mass transfer during primary drying. However, the higher total pressures also reduce the magnitude of the bulk diffusivity of the gas mixture, and combined with the smaller Knudsen diffusivity of TBA, these pressures could significantly affect the competing mass transfer mechanisms during freeze-drying. The thermodynamic method and analysis developed in this work are useful in their own physicochemical importance and also provide a necessary component for a new class of freeze-drying mathematical models. Moreover, they could provide a general modeling approach for predicting the vapor pressures of multicomponent vapor mixtures in equilibrium with their frozen solid mixtures.
- Freeze-drying
- Water
- tert-Butyl alcohol (TBA)
- Thermodynamic modeling
- UNIFAC (Dortmund)
- Partial vapor pressures
- Knudsen diffusion
- Bulk diffusion
- Convective flow
- © PDA, Inc. 2019
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