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Abstract
We carried out the formulation set-up and thermodynamics as well as morphological characterization of two systems: an aqueous-based formulation and an organic-solvent-based formulation with tert-butanol (TBA) at eutectic composition (20% TBA + water 80% by mass) containing ibuprofen as the model pharmaceutical active component. The goal was to carry out the optimization of a soft freeze-drying cycle for heat-sensitive drugs. The organic-based ibuprofen formulation had a glass transition temperature significantly higher compared to that of the aqueous-based ibuprofen formulation, which allowed much higher sublimation temperatures for these systems in comparison with the pure water-based ibuprofen formulations. The morphological study of the frozen organic-based formulation showed unexpected behavior in comparison with previous literature data reported for water-based formulations. For the same freezing rates, the mean diameters of the solvent crystals of organic-based formulations were much larger than that of ice crystals of aqueous-based formulation, which led to a freeze-dried matrix of higher permeability. In contrast to what was observed with the aqueous-based formulations, the freezing rates, in the range of classical industrial values investigated, had no significant effect on the supercooling of the liquid ibuprofen formulations tested as well as on the nucleation temperatures and on the morphology of the organic solvent crystals. All these singular characteristics, with lower sublimation enthalpies and higher equilibrium vapor pressure values previously measured with the same formulations in our laboratory, explain the large reduction of sublimation times observed during the soft freeze-drying processes for heat-sensitive drugs with organic (TBA)-based formulations.