No abstract

This paper describes the main thermodynamic concepts related to the construction of supplemented phase (or state) diagrams (SPDs) for aqueous solutions containing vitrifying agents used in the cryo-and dehydro-preservation of natural (foods, seeds, etc.) and synthetic (pharmaceuticals) products. It also reviews the empirical and theoretical equations employed to predict equilibrium transitions (ice freezing, solute solubility) and non-equilibrium transitions (glass transition and the extrapolated freezing curve). The comparison with experimental results is restricted to carbohydrate aqueous solutions, because these are the most widely used cryoprotectant agents. The paper identifies the best standard procedure to determine the glass transition curve over the entire water-content scale, and how to determine the temperature and concentration of the maximally freeze-concentrated solution.

Supplemented temperature/composition phase diagrams include the non-equilibrium glass-transition temperature (T g ) curve and equilibrium ice-melting and solubility curves. The inclusion of the non-equilibrium curve allows one to establish relationships with the time coordinate and, thus, with the dynamic behavior of systems, provided that the thermal history of such systems is known.The objective of this report is to contribute to the potential applications of supplemented state diagrams for aqueous glass-formers, in order to describe the influence of water content, nature of vitrifying agents, and temperature on the physico-chemical properties of foods and biological and pharmaceutical products. These data are helpful to develop formulations, processing strategies, or storage procedures in order to optimize the stability of food ingredients and pharmaceutical formulations. Reported experimental data on phase and state transitions for several food and pharmaceutical systems were analyzed. Some methodological aspects and the effect of phase and state transitions on the main potential chemical reactions that can alter those systems during processing and/or storage are discussed.

No abstract

No abstract

The purpose of this work was to investigate the phase behavior of tertiary butanol (TBA) and volatile ammonium salts in frozen mixtures with some commonly used excipients and the efficacy of such volatile additives in accelerating the sublimation of ice from frozen solutions. Differential scanning calorimetry was employed to determine first-order phase transformations and glass transition temperatures in binary and ternary mixtures. Ice sublimation rates were studied by conventional freeze-drying and mass loss with time. A eutectic temperature (268 K) was identified for the anhydrous TBA-sucrose system. In frozen ternary water-excipient-TBA systems, the relative amplitudes of the glass and phase transitions, as measured during warming scans, were found to depend critically on the previous cooling rates. Glass transitions of all the freeze-concentrated mixtures used were determined. The sublimation studies indicated an ability of all volatile additives to accelerate ice sublimation from amorphous, freeze-concentrated solutions, but no clear ranking order, applicable to all systems studied, could be established.

Freeze-drying, in the past popular in the food industry, has more recently been adopted by the pharmaceutical industry as a standard method for the production of stable solid preparations. Freeze-drying of Pharmaceuticals and Biopharmaceuticals is the first book to specifically describe this process, as related to the pharmaceutical industry. The emphasis of this book is on the properties of the materials processed, how effective formulations are arrived at, and how they are stored and marketed. Beginning with a historical overview of the process, Freeze-drying of Pharmaceuticals and Biopharmaceuticals briefly describes the processes and equipment involved, including: the physics, chemistry and biochemistry associated with freezing, aspects of formulation development, primary and secondary drying; the economics and engineering of scaling up; and, most importantly, attributes of the dried product. It also discusses in detail the science behind freeze-drying, such as the properties of crystalline and amorphous solids. The book concludes with selected case studies and discusses the future of freeze-drying, advances in alternative drying methods, and concludes with an extensive bibliography. This book, written by a leading expert in the field, is aimed primarily at product and process developers in the biopharmaceutical industry and academia.

No abstract