Secondary drying water content effects

At the completion of primary drying, the water content of an amorphous product is sometimes expressed as JVg g water per g solid. The actual value, typically 0.3-0.5 g g is governed by details of the freezing process and will vary from product to product, or even from vial to vial. For most practical purposes, however, it may be assumed that the water content has little or no effect on secondary drying. This... 

Pikal et al studied a 5%-povidone (polyvinyl pyrrolidone, PVP) solution, dried from an 8-ml fill volume, of 2-cm depth, and from a 4-ml fill volume at a 1-cm fill depth. In this instance, the fill depth had little effect on the specific surface area of the dried product (2.5 m g compared to 2.3 m g )- It was found that the rates of secondary drying (as measured by the mean ratio of the (1 - F) values), the normalised water contents of the two products were essentially identical. A mean ratio of (1 - F) of 1.19 0.17 was found, indicating that cake thickness did not significantly affect secondary drying kinetics. It can thus be concluded that material at the top of the cake dries at a similar rate to material at the bottom, provided overheating is avoided. Similar experiments were carried out on an amorphous, formulated moxalactam product, as shown below. 

Factors that favor salt partitioning decrease selectivity for the large alkali metal cations. As shown in Table 20, by far the most important solvent property required to attain good Cs ion selectivity is weak basicity. All other effects are secondary. These include solvent acidity, molar volume, and water content. Solvent polarity as measured by the dielectric constant and the solvatochromic parameters tt and Er actually plays a negligible role in controlling selectivity. With regard to the presence of water in the system, a dry solvent, namely one that itself dissolves water poorly, represents the preferred choice. But, in fact, a dry solvent also tends to have weak basicity. To enhance Cs ion selectivity also requires the avoidance of ion pairing, especially for small counteranions. 

The protective effect is dependent on the process conditions. Especially the product temperature during secondary drying seems to be a critical parameter for survival. As the protective effect only occurs for low residual water contents when structural water is already removed, the water replacement mechanism may play a role in protecting cells from desiccation damage. In order to further investigate the mechanism of protection, pulsed NMR measurements were carried out to measure proton mobility of samples with and without added protectant. 

The well-known secondary a-relaxation often associated with proton mobility is also observed in CS (neutralized and nonneutralized) from 80 °C to the onset of degradation. On minimum moisture content conditions, this relaxation process could be noticed in the whole temperature range before the onset of thermal degradation. It is strongly affected by moisture content for dry samples by water effects, the activation energy shifts to lower values when compared to dry annealed samples. The nonneutralized CS showed an easier mobility in this ion motion process. This relaxation process exhibits a normal Arrhenius-type temperature dependence with activation energy of 80-90 kJ/mol. 

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