Glass transition freeze-dried systems

In addition to characterizing frozen systems intended to be freeze dried, it is important to characterize the freeze-dried product. This includes determination of the physical state of the dried product that is, crystalline, partially crystalline, or amorphous. It may also include identification of the polymorph of a crystallizing component which exhibits polymorphism and determination of whether the crystal form observed is affected by changes in formulation and processing conditions. For amorphous systems, the glass transition temperature of the amorphous solid, as well as the extent to which Ts changes with residual moisture, may be a critical attribute of the product with regard to both physical and chemical stability. 

Glass transitions, both in frozen systems and in freeze-dried solids, can be difficult to detect. This may be caused by the small heat capacity change associated with the glass transition, a broad glass transition region, or both. Interpretation is made more uncertain by baseline drift or other noise. In addition, other thermal events at temperatures close to the glass transition, such as enthalpy recovery or crystallization, may disguise the heat capacity... 

Freeze-dried protein formulations are amorphous systems, at least in part, and the physical and chemical behavior of such products depends on the characteristics of amorphous systems, perhaps as much as their behavior depends on the unique behavior of proteins. Amorphous materials below their glass transition tempera-... 

Particularly for freeze-dried products, formulation and process are interrelated. Properties of the formulation, in particular the collapse temperature, will have a significant impact on the ease of processing. An efficient process is one that runs a high product temperature. However, the temperature cannot be too high or product quality will be compromised. As the glass transition temperature depends on chemical composition of the amorphous phase, Tg and collapse temperature are strongly formulation dependent. Collapse temperatures for common excipient systems vary from less than —50°C to around —10°C (Table 2). 

The glass transition as a reference state can be used to explain all transformation in time, temperature, and structure composition effects between different relaxation states for technologically practical food systems in their nonequilibrium nature. Among others, specific examples include reduced activity and shelf stability of freeze-dried... 

The results of DSC analyses of freeze-dried plum (skin and pulp at the natural proportion) presented different behaviors for each domain. At Uy, 0.75, two glass transitions (Tg) were visible (Figure 58.1a) as a deviation in base line and shifted toward lower temperatures with increasing moisture content and caused by the plasticizing effect of water (Slade and Levine, 1991). The first one, clearly visible at lower temperatures, was attributed to the glass transition of a matrix formed by sugars and water. The second one, less visible and less plasticized by water, was probably caused by macromolecules of the fruit pulp. Two Tg are normally visible in systems formed by blends of polymers (Verghoogt et al., 1994) and in edible films (Sobral et al., 2002) caused by phase separation between polymers and between proteins and plasticizers, respectively. However, Sobral et al. (2001) and Telis and Sobral (2002) also observed two Tg for persimmon and tomato, respectively, at low domain. 

Measurement of the glass transition of frozen solution formulation of the candidate drug is an important preformulation determination, since freeze-drying an amorphous system above this temperature can lead to a decrease in viscous flow of the solute (due to a decrease... 

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