Hydration amorphous solids

A high percentage 01 water remains after the sublimation process, present as adsorbed water, water of hydration or dissolved in the diy amorphous solid this is difficult to remove. Usually, shelf-temperature is increased to 25 to 40°C and chamber pressure is lowered as far as possible. This stiU does not result in complete diying, however, which can be achieved only by using even higher temperatures, at which point thermally induced product degradation can occur. 

Commonly an amorphous solid may have solubility in both aqueous and DMSO that is over 100 hmes higher than any of the crystalline forms. An amorphous solid can be inadvertently created from a crystalline material, e.g. by heating a crystalline hydrate or solvate for a short time period below its melhng point in a drying pistol. 

It is the objective of this chapter to discuss the various mechanisms whereby water can interact with solid substances, present methodologies that can be used to obtain the necessary data, and then discuss moisture uptake for nonhydrating and hydrating crystalline solids below and above their critical relative humidities, for amorphous solids and for pharmaceutically processed substances. Finally, transfer of moisture from one substance to another will be discussed. 

Both the dimer and the photohydrate from photolysis of uracil have been isolated not only as spots on a chromatogram7 but also as crystalline or amorphous solids—the dimer by Smietanowska and Shugar45 and Swenson and Setlow48 and the hydrate by Gattner and Fahr.45 Many physical properties have not been recorded for these materials. The melting points of the principal dimer is 380°.34 The infrared spectrum is not reported. The elementary composition of the hydrate has been reported.45 ... 

In general, hydrated borates of heavy metals are prepared by mixing aqueous solutions or suspensions of the metal oxides, sulfates, or halides and boric acid or alkali metal borates such as borax. The precipitates formed from basic solutions are often sparingly-soluble amorphous solids having variable compositions. Crystalline products are generally obtained from slightly acidic solutions. 

Guillory, J. K. (1999). Generation of polymorphs, hydrates, solvates, and amorphous solids. In Physical characterization of pharmaceutical solids (ed. H. G. Brittain), pp. 183-226. Marcel Dekker, New York. [254]... 

C-Phycocyanin is abundant in blue-green algae. Nearly 99% deuterated samples of this phycobiliprotein were isolated from the cyanobacteria that were grown in perdeuterated cultures [46] (99% pure D2O) at Argonne National Laboratory. This process yielded deuterated C-phycocyanin proteins (d-CPC) that had virtually all of the H—C bonds replaced by H—C bonds. One can obtain a lyophilized sample that is similar to amorphous solids as determined by neutron diffraction [43]. As it has been defined in previous papers [47-49], the level of hydration h = 0.5 corresponds to 100% hydration of C-phycocyanin, which leads to a coverage of about 1.5 monolayers of water molecules on the surface of the protein [50]. 

The amount of moisture sorbed by amorphous solids is typically much greater than that sorbed by non-hydrating... 

A particular solvate is hydrate, in which water molecules form a solid adduct to the parent compound. Hydrate may not be stable below a certain water level, and may lose its water molecule and form anhydrous crystalline or amorphous solids. Above the crossover water level, hydrate is stable and always has lower solubility than the anhydrous solid (Khankari 1995). 

The Sb Mossbauer parameters (79) of tin-antimony oxides calcined at 600°C were related to the preparative procedure. The white precipitates, formed in alkaline media that contain hydrated tin(IV) and antimony(V) species, were considered to dehydrate after 16-hr calcination at 600°C to give blue, poorly crystalline, highly defective rutile type solids. The Mossbauer spectra revealed the presence of tin(IV), antimony(V), and anti-mony(III) species in oxygen environments and were consistent with the dehydration process inducing the reduction of antimony(V) as is observed in the pyrolysis of antimonic acid (26) and the transformation of the tin(IV) hydroxide gel to tin(IV) oxide (30). The coexistence of random arrays of such units in a noncrystalline monophasic solid is consistent with the X-ray diffraction study (72) that described these materials as single-phase amorphous solids. 

The Hydration Limit of Amorphous Solids and Long-Term Stability... 

The effect of "residual water" on either protein stability or enzyme activity continues to be a topic of great interest. For example, several properties of lysozyme (e.g., heat capacity, diamagnetic susceptibility (Hageman, 1988), and dielectric behavior (Bone and Pethig, 1985 Bone, 1996)) show an inflection point at the hydration limit. Detailed studies on the direct current protonic conductivity of lysozyme powders at various levels of hydration have suggested that the onset of hydration-induced protonic conduction (and quite possibly for the onset of enzymatic activity) occurs at the hydration limit. It was hypothesized that this threshold corresponds to the formation of a percolation network of absorbed water molecules on the surface of the protein (Careri et al., 1988). More recently. Smith et al., (2002) have shown that, beyond the hydration limit, the heat of interaction of water with the amorphous solid approaches the heat of condensation of water, as we have shown to be the case for amorphous sugars. 

Though there have been significant advances in the sophistication of longterm stability predictions (i.e., beyond a simple Tg-based approach), the hydration limit continues to be an active area of research in our and others laboratories. The hydration limit may be related to the temperature of "zero mobility" and that the use of the temperature dependence of the hydration limit has shovm some promise as a quantitative approach to determine the effect of residual water on the long-term stability of amorphous solids. 

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