https://onlinelibrary.wiley.com/doi/pdf/10.1021/js9601896

Characteristics and Significance of the Amorphous State in Pharmaceutical Systems

Amorphous pharmaceutical solids: preparation, characterization and stabilization.

Numerous organisms are capable of surviving more or less complete dehydration. A common feature in their biochemistry is that they accumulate large amounts of disaccharides, the most common of which are sucrose and trehalose. Over the past 20 years, we have provided evidence that these sugars stabilize membranes and proteins in the dry state, most likely by hydrogen bonding to polar residues in the dry macromolecular assemblages. This direct interaction results in maintenance of dry proteins and membranes in a physical state similar to that seen in the presence of excess water. An alternative viewpoint has been proposed, based on the fact that both sucrose and trehalose form glasses in the dry state. It has been suggested that glass formation (vitrification) is in itself sufficient to stabilize dry biomaterials. In this review we present evidence that, although vitrification is indeed required, it is not in itself sufficient. Instead, both direct interaction and vitrification are required. Special properties have often been claimed for trehalose in this regard. In fact, trehalose has been shown by many workers to be remarkably (and sometimes uniquely) effective in stabilizing dry or frozen biomolecules, cells, and tissues. Others have not observed any such special properties. We review evidence here showing that trehalose has a remarkably high glass-transition temperature (Tg). It is not anomalous in this regard because it lies at the end of a continuum of sugars with increasing Tg. However, it is unusual in that addition of small amounts of water does not depress Tg, as in other sugars. Instead, a dihydrate crystal of trehalose forms, thereby shielding the remaining glassy trehalose from effects of the added water. Thus under less than ideal conditions such as high humidity and temperature, trehalose does indeed have special properties, which may explain the stability and longevity of anhydrobiotes that contain it. Further, it makes this sugar useful in stabilization of biomolecules of use in human welfare.

The role of vitrification in anhydrobiosis.

Publisher Summary This chapter focuses on “food polymer science” approach and illustrates various recent examples of the way it has been used to define structure–function relationships in food products and processes and to assess and understand the effects of glass transitions and water plasticization on food quality, safety, and stability. The chapter reviews some theoretical principles from the field of synthetic polymer science that have been shown to be applicable to the studies of the glassy state phenomenon in foods and illustrates those applications by means of a broad overview focusing primarily on the most recent experimental studies by a number of groups that have been especially active in this rapidly growing field of research. The results of such studies have demonstrated the major opportunity offered by the food polymer science approach to expand not only the quantitative knowledge but also, of broader practical value in the context of industrial applications, the qualitative understanding of food products and processes with respect to (1) structure–functional property and water relationships and (2) the influences of nonequilibrium glassy and rubbery states on time-dependent mechanical and rheological properties related to quality and storage stability.

T. Arakawa

Papers

Interactions of Stabilizers with Proteins During Freezing and Drying.