Anhydrous phases

The phase transformation relationships for the solvatomorphs of naproxen sodium have been reported [71], The dihydrate phase is obtained upon crystallization from water, and a monohydrate phase could be prepared by the dehydration of the dihydrate phase in a desiccator (RH = 0%) for two days. The anhydrate phase could be obtained from either the monohydrate or dihydrate by drying the substance in an oven at 120 °C for two hours. Thermal analysis data was used to demonstrate the existence of two types of water in the dihydrate phase, and that each could be removed at a characteristic temperature. 

The hydration equilibria and phase transformations associated with a cytotoxic drug, BBR3576, have been studied [72]. The initially hydrated form could be made to undergo a phase transition where it lost approximately half of its water content, but the hemidesolvated product could be easily rehydrated to regenerate the starting material. If however, the original sample was completely dehydrated, the substance first formed a metastable anhydrate phase that underwent an irreversible exothermic transition to a new anhydrate crystal form. The hydration of this latter anhydrate form yielded a new hydrate phase whose structure was different from that of the initial material. 

It has been found that both the anhydrous Form III and dihydrate phases of carbamazepine exhibit fluorescence in the solid state [78]. The fluorescence intensity associated with the dihydrate phase was determined to be significantly more intense than that associated with the anhydrate phase, and this difference was exploited to develop a method for study of the kinetics of the aqueous solution-mediated phase transformation between these forms. Studies were conducted at temperatures over the range of 18 40 °C, and it was found that the phase transformation was adequately characterized by first-order reaction kinetics. The temperature dependence in the calculated rate constants was used to calculate activation energy of 11.2 kCal/ mol (47.4 cal/g) for the anhydrate-to-dihydrate phase conversion. 

The formation of niclosamide hydrates, and the effect of relative humidity on the solvatomorphs obtained from acetone and ethyl acetate has been studied [79], The acetone and ethyl acetate solvatomorphs could be desolvated, and exposure to elevated humidity resulted in the formation of two hydrate structures. Each hydrate could be dehydrated into a different anhydrate phase, but only the hydrate formed from the acetone desolvate could be rehydrated to form a hydrate phase. Dynamic vapor sorption has been used to develop a method for determining the onset relative humidity of a glass transition and associated crystallization process [80]. 

X-ray powder diffractometry can be used to study solid state reactions, provided the powder pattern of the reactant is different from that of the reaction product. The anhydrous and hydrated states of many pharmaceutical compounds exhibit pronounced differences in their powder x-ray diffraction patterns. Such differences were demonstrated earlier in the case of fluprednisolone and carbamazepine. Based on such differences, the dehydration kinetics of theophylline monohydrate (CvHgN H20) and ampicillin trihydrate (Ci6H19N304S 3H2O) were studied [66]. On heating, theophylline monohydrate dehydrated to a crystalline anhydrous phase, while the ampicillin trihydrate formed an amorphous anhydrate. In case of theophylline, simultaneous quantification of both the monohydrate and the anhydrate was possible. It was concluded that the initial rate of this reaction was zero order. By carrying out the reaction at several... 

When drug polymorphs cannot interconvert as a result of being suspended in aqueous solution, a different bioavailability of the two forms usually results [126], For instance, the peak concentration of chloramphenicol in blood serum was found to be roughly proportional to the percentage of the B-polymorph of chloramphenicol palmitate present in a matrix of the A-polymorph [133]. The same concept has been found to apply to hydrate species, where the higher solubility and dissolution rate of the anhydrous phase relative to the trihydrate phase resulted in measurably higher blood levels when using the anhydrate as... 

The molecular packing in the monohydrate phase is fundamentally different from that of the anhydrate phase, as shown in Fig. 7.8 [18]. 

Fig. 7.4. Conformation of the theophylline molecule in the anhydrate phase [18], used with permission, and in the monohydrate phase [20].

The commercially available form of Aspartame is hemihydrate Form II, which transforms into hemihydrate Form I when milled, and a 2.5-hydrate species is also known [57,58]. XRPD has been used to study the desolvation and ultimate decomposition of the various hydrates. When heated to 150°C, both hemihydrate forms dehydrate into the same anhydrous phase, which then cyclizes into 3-(carboxymethyl)-6-benzyl-2, 5-dioxopiperazine if heated to 200°C. The 2.5-hydrate was shown to dehydrate into hemihydrate Form II when heated to 70°C, and this product was then shown to undergo the same decomposition sequence as directly crystallized hemihydrate Form II. 

Portland cement, which was discovered in 1824, sets from within. It is made by firing limestone ( 75%) with clays at about 1450 °C, causing partial fusion and the formation of a clinker, which is then powdered. This material typically contains the equivalents of about 67% CaO, 22% SiC>2, 5% AI2O3, 3% Fe2C>3, and the balance other materials, and the four chief components are the following anhydrous phases ... 

A knowledge of the relevant high-temperature phase equilibria is necessary for understanding the factors that govern acceptable bulk compositions for Portland cement clinker, the conditions under which the latter can be manufactured, and the phase composition and microstructure of the resulting material. This chapter deals with these equilibria and with the phases to which they relate, with the exception of the major clinker phases, which were described in Chapter I. Some anhydrous phases primarily of interest in relation to other types of cement are also considered here. Principles underlying the preparation of anhydrous silicate, aluminate and other high-temperature phases are outlined. 

Other foreign ions in the anhydrous phases, and the extents to which they tend to pass into the pore solution on hydration. If the C-S-H constituent of the gel is assumed to have the same Ca/Si ratio as in calcium silicate pastes, one would expect that the ratio would be about 1.9 (Si/Ca = 0.53) in a gel with Al/Ca = 0.07. This agrees with some, but not all, of the data in Table 7.1. The hypothesis might explain the observations of Rayment and Lachowski (R29) on the bimodal distribution of Ca/Si ratio in the in situ gel and the relative constancy of its Ca/(Si + Al) ratio. It probably offers the most satisfactory explanation of the existing data but needs to be further tested. Continued studies by TEM of ion-thinned sections may be expected to yield valuable data in this respect. 

When the anhydrous phases dissolve, the species present in solution in significant concentrations are Ca, Al(OH)4" and OH CaOH may be ignored. Taking CjAHg as an example, the equilibrium with solution is thus represented by the equation... 

The interlayer separation directly depends on the number of water molecules present between the layers. In the anhydrous phases ZrM(P04)2 (M = Mg, Ca, Sr, or Ba) and the half exchanged phases ZrHM(P04)2 (M = Li, Na, K, Rb, or Cs) the interlayer separation is independent of cation size, indicating that the interlayer cavity, which contains one water molecule in the unexchanged compound, is sufficiently large to accommodate a single cation. In contrast, in the fully exchanged alkali metal ion compositions, the interlayer separation increases with increasing cation radius. 

The Cl chondrites represent one of the most curious paradoxes of cosmochemistry. Despite their unfractionated compositions, the Cl chondrites are the most altered of all chondrites, with water contents of —19.5 wt.% (Nagy et al., 1963). Anhydrous phases (olivines and pyroxenes) represent less than 1 vol.% of these meteorites (Leshin et al., 1997). Cl chondrites are complex meteorites that consist of a dark, fine-grained matrix comprised of phyllosilicates with magnetite, sulfides, carbonates, and sulfates embedded within it (e.g., DuFresne and Anders, 1962 Nagy, 1966). They have experienced extensive breccia-tion on their asteroidal parent bodies that caused... 

Figure 13 A 5 jjim interplanetary dust particle. This is a carbon-rich particle with chondritic elemental composition. It is porous and entirely composed of anhydrous phases. This 10 ° g particle is an aggregate of >10 umelated and unequilibrated grains. The smooth grains are t5fpically single mineral grains such as Fo, En, or pyrrhotite or carbonaceous material, and the <0.5 p,m lumpy grains are usually GEMSs. This is a relatively t5fpical example of the particles that have entry speeds consistent with cometary origin.

Ryabchikov, 2000)—or it may dissolve into nominally anhydrous phases. 

Figure 12 Molar compositions of phases in the system MgO AI2O3 Si02-H20, projected from H2O into the Mg0-Al203-Si02 ternary. Solid circles are anhydrous phases, open circles are hydrous phases. Abbreviations as in Table 1. The shaded box represents plausible mantle peridotite compositions, with the upper hound being at —5 wt.% AI2O3.

Since the 1960s, there has been accumulating evidence that mantle-derived NAMs contain measurable amounts of water —on the ppm to thousands of ppm level. This leads to the intriguing possibility that the major hosts for water in the Earth s mantle are these nominally anhydrous phases, rather than conventional hydrous minerals with stoichiometric OH (Bell and Rossman, 1992a). 

In another example, Richard et al. (2002) simulated the transport of water in a two-dimensional mantle convection model. They found that mantle flow, not diffusion, was the primary control on water distribution, which led to a homogeneous distribution of water in the mantle. If this is the case, the transition zone may contain less water than could be dissolved into the nominally anhydrous phases present there. Because of the low solubility of water in lower-mantle nominally anhydrous phases (Bolfan-Casanova et al., 2000), Richard et al. proposed that there might be a water-rich fluid phase in the lower mantle. They did not, however, consider the possibility of water-induced partial melting, leading to a melt rather than a fluid. 

The ampicillin molecule exists as a zwitterion in both forms, with the overall molecular configuration being fairly similar as well. The structural differences induced by the presence of the water molecules in the trihydrate phase are evident in the differing configurations of the respective thiazolidine rings, where more planarity is found for the trihydrate phase than is found for the anhydrate phase. It was deduced that... 

When the FTIR spectra of polymorph systems differ substantially, the results may readily permit the identification of a particular form. For instance, the two forms of ranitidine hydrochloride yielded spectra that differed in the region above 3000 cm and in the regions spanning 2300-2700 cm and 1570-1620 cm b Zanoterone has been found to crystallize in a number of different forms, each of which yields a characteristic infrared spectrum. When solvent molecules are incorporated in a crystal lattice, the new structure is often sufficiently different from that of the anhydrous phase so that many of the molecular vibrational modes are altered. 

When the hydrates or solvates of a given compound are stable with respect to phase conversion in a solvent, the equilibrium solubility of these species can be used to characterize these systems. For instance, the equilibrium solubility of the trihydrate phase of ampicillin at 50° C is approximately 1.3 times that of the more stable anhydrate phase at room temperature. However, below the transition temperature of 42°C, the anhydrate phase is more soluble and is therefore less stable. 

When theophylline monohydrate was dehydrated, it formed a metastable anhydrous phase, which then transformed to the stable anhydrate. The XRD patterns of the two anhydrate phases and the monohydrate were sufficiently different so that all three of them could be simultaneously identified in a sample (Fig. 7A). Anhydrous theophylline was granulated with an aqueous solution of PVP. During the wet-massing stage, the anhydrate transformed to the monohydrate. When the granules were dried, there was dehydration resulting in the formation of the metastable anhydrate, which then transformed to the stable... 

The phase transitions of theophylline monohydrate were discussed earlier in the section dealing with Phase Transitions Induced During Processing (Fig. 7). High temperature XRD was used to investigate the dehydration of theophylline monohydrate (Fig. 11). This technique revealed that dehydration resulted in a metastable anhydrous phase, which then transformed to the stable anhydrate. Theophylline has been in widespread use for many years and its solid-state properties have been the subject of numerous investigations. Without high temperature XRD, it is unlikely that this metastable phase would have been identified. 

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