In this review we describe thermodynamic properties of small carbohydrates with an emphasis on characteristic aspects of α, α -trehalose, which are physicochemical background of its superior biological protective function. First, aqueous properties of small carbohydrates are discussed in terms of unfrozen water and partial molar isentropic compressibility, being related to their glass transition temperatures. It is argued for these thermodynamic parameters that there exists a common systematic dependency on molecular structures of carbohydrates. Next solid-state properties of α, α -trehalose are discussed in view of humid effects on its phase transition behavior. One of its known anhydrates, T_α, can be formed only under dry atmospheres, of which high hygroscopicity would contribute to avoiding the devitrification of the sugar glass induced by moisture uptake. Another interesting finding is that the anhydrate T_β is formed at as low as 95℃ under high humid atmospheres whereas dry or intermediate humid atmospheres give the anhydrate T_β over 160℃. A picture is provided, which depicts pathways to link various solid forms of trehalose with taking into account the humid effects.

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Brief account is made on the supercooling and glass formation behavior of various liquids of low molecular weights. Special emphasis is placed on aqueous solutions because of their importance for cryopreservation of living cells and biotechnology at low temperatures. It is shown that there are two empirical relations in supercoolings of aqueous solutions: (1) Linear relation between T_H (homogeneous ice nucleation temperature) and T_m (melting temperature), and (2) Additivity rule holds in supercooling.

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Preparation and evaluation procedures of amorphous drugs are reviewed. Amorphous drug as a pharmaceutical dosage form of poorly water-soluble drug has been investigated to improve the dissolution property in spite of the stability problem. Glass transition temperature (Tg) of the amorphous form is a good index to evaluate the stability of the drug during storage. As a recent advance in technology, many evaluation procedures have been developed to identify the amorphous state. Amorphous forms are possible to prepare by many methods, such as milling, supercooling, spray-drying and freeze-drying. Drug adsorption into porous material is also an effective way to make the amorphous form. Cefditroren pivoxil, chenodeoxycholic acid and thoxyphenylacetyltylosin (MAT) and the physicochemical properties are introduced as examples for the amorphous forms of drugs.

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Solid dispersions of drug in polymers are widely used to obtain the amorphous state of materials. However amorphous is unstable and easily crystallized. An estimation method for the physical stability of amorphous drug and a clarification of the effect of polymer on crystallization of amorphous drug in solid dispersion are primarily required. Generally solid dispersions were containing different ratios of drug and polymers, e.g. Polyvinylpyrrolidone (PVP), Hydroxypropylmethylcellulose (HPMC). The physical stability of solid dispersion was evaluated by the induction period of the crystallization under isothermal condition. The induction period of crystallization from amorphous drug was gradually delayed with increasing amounts of polymer. The crystallization of drug was prevented by the present of polymer. Drug-polymer interaction was recognized as one of the central cause, and the FT-IR spectra of solid dispersion suggested the interaction between drug and polymer. In spite of no interaction between Flurbiprofen and PVP, the solid disperseon containing them was stable. It is noted that the interfacial free energy between drug crystal and supercooled liquid and the activation energy of diffusion of drug molecules which related to nucleation was closely related to the drug crystallization. In the case of tolbutamide or flurbiprofen and PVP, the interfacial free energy was not affected by PVP contents. The activation energy of diffusion was increased with increase the PVP contents in the solid dispersion, suggesting that the crystallization of TB in solid dispersion would be affected by the diffusivity of drug. On the other hand, in the solid dispersion of FBP, the activation energy of diffusion was not changed by PVP contents. These reports suggested that the retardation of crystallization of drug induced by the coexistense of polymer could be related to the interaction between drug and polymer and the increase of the activation energy of diffusion.

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Preserving the native conformation of protein during freeze-drying would lead to a greater stability against denaturation during storage. A number of investigators have reported that freeze-drying in the presence of sugar aids in preserving the native conformation of a protein. When a protein solution is freeze-dried in the presence of sugars, amorphous matrices of sugars are formed, which could embed protein molecules. The embedding of protein molecules in the amorphous sugar matrices is generally thought to prevent conformational changes in the protein during dehydration and storage due to interactions between protein and sugar molecules. In this review we describe the methods which are used to study the sugar-protein hydrogen bond. The effects of various sugars on the structural stabilization of protein in the dried state are also reviewed and discussed.

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Glassy materials are usually hard, have low specific heat, and molecules in glassy state are less mobile than those in rubbery state. Glass transition point, Tg, can be obtained by several methods, such as by the measurement of viscoelasticity by DMTA, change in specific heat by DSC, or FID by NMR. There are not so many research works that compared Tgs obtained by these methods. However, from the studies on Tgs of glucose syrup with small amount of k-carrageenan and amylopectin that compared them, Tgs obtained by these methods differed by 5-30℃, Tg obtained by NMR being the lowest and that obtained by DMTA being the highest. It seems that NMR measurement is more sensitive for the change in molecular mobility, while DMTA monitors more macroscopic change in the system. Each measurement has its merits and demerits. DSC measurement requires less amount of sample, but it is sometimes difficult to detect the change in specific heat. The information of molecular mobility can be obtained by NMR measurement. DMTA measurement requires larger amount of sample, and sample molding is generally necessary. In addition, water content may change during heating. However, DMTA is quite sensitive to the change in viscoelasticity of a sample. Food is a complicated multi-component system, and various changes occur during heating that sometimes makes it difficult to detect Tg. More systematic works would be necessary to understand glassy state of food.

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Recently, a glass transition concept has been introduced in the field of food science. According to the concept, it is believed that many kind of food material are in amorphous state, and their transitional change such as glass transition affects food stability. The amorphous state below Tg is, however, defined as nonequilibrium from a thermodynamical point of view. This also suggests that an amorphous food is not always stable within a practical long storage time. In this paper, the amorphous starch prepared by ball-milling, which is an example of amorphous food materials, shows an enthalpy relaxation as same as that prepared by melt quench method. Furthermore, the correlation between the enthalpy relaxation and moisture absorption property for the amorphous starch is discussed.

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Effect of the glass transition in various freeze-dried amorphous food systems on the rate of Maillard reaction was summarized in this review. The rate of Maillard reaction of amino acid and reducing sugar embedded in an amorphous matrix by freeze-dry shows a remarkable change at the glass transition temperature (T_g), that is, the reaction rate below the T_g becomes much slower than that above the T_g. Maillard reaction, however, progresses on the scale of several days even in the glassy matrix below the T_g, although the molecular diffusivity is limited enough in the glassy state. From results of our systematic studies on the rate of Maillard reaction of six kinds of reducing sugar (i.e., ribose, arabinose, xylose, galactose, glucose, and maltose) and lysine embedded in various glassy matrices, it was suggested that the reaction rate in glassy matrix was affected not only by the molecular mobility of matrix and/or Maillard reactants, but also by the forming of hydrogen-bond among them.

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