Freeze-Drying of an Active Principle Ingredient Using Organic Co-Solvent Formulations: Influence of Freezing Conditions and Formulation on Solvent Crystals Morphology, Thermodynamics Data, and Sublimation Kinetics

Abstract

We have investigated principally the influence of organic solvent concentration of the formulation corresponding to water +tert-butanol (TBA) mixtures and of the freezing rates on solvent crystals morphology on some thermodynamical properties (vapor pressures and sublimation enthalpies) and on sublimation kinetics. The solvent crystals’ morphology of frozen formulations showed unexpected behavior compared with the previous literature data reported for water-based formulations. Indeed, the super cooling degrees decreased by increasing the freezing rates and, consequently, the mean sizes of solvent crystals increased with the freezing rates. Otherwise, at the eutectic composition, namely at 90% (w/w) of TBA, we observed that the equilibrium vapor pressure data for solid-vapor system (sublimation) were twice higher than the data obtained with pure water systems. Moreover, the sublimation enthalpy values of organic formulations were only a quarter to a third of that of pure water. These specific thermodynamical data explained principally the faster sublimation kinetics observed during freeze-drying of our active principle ingredient (API) with TBA co-solvent formulations.