Thermophysical properties of aqueous and frozen states of BSA/water/Tris systems.

In the modelling and the optimization of pharmaceutical protein freeze-drying processes, thermophysical properties values of the formulation in frozen or in liquid states are necessary in order to determine the optimal operating conditions (temperature, pressure) of the two steps (sublimation, desorption) drying diagramme and the optimal storage conditions of the final freeze-dried product. The most important thermophysical properties of BSA/water/Tris system buffered with Tris-HCl (5%, w/w) at pH 7, a standard formulation largely used in industrial freeze-drying process of pharmaceutical proteins, are reported in this paper. The state diagram of this formulation was determined by modulated temperature differential scanning calorimetry (MTDSC) and, then the vitreous transition temperatures were interpreted as a function of water content by the Gordon-Taylor equation. The same technique was used to experimentally determine the heat capacity of the BSA/water frozen system. Moreover, the transient hot wire probe method was used to measure the thermal conductivity of the frozen system as a function of temperature. It proved that the thermal conductivity and the apparent heat capacity values for this dilute formulation were reasonably close to the values for the pure water/ice system. Sorption isotherms data were also measured by two different methods-the equilibrium with saturated salts solutions and also the controlled humidity oven. Water vapour sorption data were finally correlated by the three parameters Guggenheim, Anderson, De Boer (GAB) equation.