Raman crystalline hydrates

Spectroscopic methods. Hydration numbers have been inferred from comparisons of the characteristics of the absorption and the Raman spectra of lanthanide ions in aqueous solution and in crystalline hydrates of known structure (Freed 1942, Krumholz 1958). For the region of 9/2 transitions in... 

Faraday is liberated at the cathode. Moreover, it has been recently shovvn that these solutions give infrared and Raman spectra closely resembling those of the crystalline hydrates containing the hydronium ion. In particular, they show clearly, especially for 30, the presence of two infrared frequencies in the O—H or O—D stretching range, which is indicative of a pyramidal rather than a planar structure. 

Other approaches use Laser-Raman spectra to differentiate five conformational states of lactose, including a-lactose monohydrate, /3-lactose, and lactose glass (Susi and Ard 1974). Differential thermal analysis has also been used to measure the concentration of crystalline lactose, especially a-lactose hydrate (Ross 1978B). The specialized equipment required by these procedures may limit their use. 

Savolainen et al. investigated the role of Raman spectroscopy for monitoring amorphous content and compared the performance with that of NIR spectroscopy [41], Partial least squares (PLS) models in combination with several data pre-processing methods were employed. The prediction error for an independent test set was in the range of 2-3% for both NIR and Raman spectroscopy for amorphous and crystalline a-lactose monohydrate. The authors concluded that both techniques are useful for quantifying amorphous content however, the performance depends on process unit operation. Rantanen et al. performed a similar study of anhydrate/hydrate powder mixtures of nitrofurantoin, theophyllin, caffeine and carbamazepine [42], They found that both NIR and Raman performed well and that multivariate evaluation not always improves the evaluation in the case of Raman data. Santesson et al. demonstrated in situ Raman monitoring of crystallisation in acoustically levitated nanolitre drops [43]. Indomethazine and benzamide were used as model... 

In essence, the test battery should include XRPD to characterize crystallinity of excipients, moisture analysis to confirm crystallinity and hydration state of excipients, bulk density to ensure reproducibility in the blending process, and particle size distribution to ensure consistent mixing and compaction of powder blends. Often three-point PSD limits are needed for excipients. Also, morphic forms of excipients should be clearly specified and controlled as changes may impact powder flow and compactibility of blends. XRPD, DSC, SEM, and FTIR spectroscopy techniques may often be applied to characterize and control polymorphic and hydrate composition critical to the function of the excipients. Additionally, moisture sorption studies, Raman mapping, surface area analysis, particle size analysis, and KF analysis may show whether excipients possess the desired polymorphic state and whether significant amounts of amorphous components are present. Together, these studies will ensure lotto-lot consistency in the physical properties that assure flow, compaction, minimal segregation, and compunction ability of excipients used in low-dose formulations. 

This review article is concerned with the structure, bonding, and dynamic processes of water molecules in crystalline solid hydrates. The most important experimental techniques in this field are structural analyses by both X-ray and neutron diffraction as well as infrared and Raman spectroscopic measurements. However, nuclear magnetic resonance, inelastic and quasi elastic neutron scattering, and certain less frequently used techniques, such as nuclear quadrupole resonance, electron paramagnetic resonance, and conductivity and permittivity measurements, are also relevant to solid hydrate research. 

Complementary investigations of solid hydrates by means of both spectroscopic methods, especially i.r. and Raman spectroscopy, and diffraction techniques enable detailed insight into structure, bonding, and dynamic processes of water molecules. There is no class of compounds which is more thoroughly studied in this respect than the crystalline... 

There is IR and Raman evidence for a phase transition for nitric acid hydrate, near 200 K.536 RAIR and ab initio calculations gave information on the structure and vibrational wavenumbers for crystalline nitric acid.537 A DRIFTS study has been performed on the interaction of gas-phase IIN03 with ice and acid (HC1, HN03) hydrate surfaces.538 An ab initio calculation of the vibrational wavenumbers of nitric acid hydrates, HN03.(Fl20)n, where n = 1, 2 or 3, has been reported.539... 

MICROSCOPIC OBSERVATION AND IN-SITU RAMAN STUDIES ON SOME SINGLE-CRYSTALLINE GAS HYDRATES UNDER HIGH PRESSURE... 

It is ideal to measure reference Raman spectra of all ingredients in their pure forms, using the same conditions as the sample. Because Raman spectroscopy is sensitive not only to molecular structure but also to the local environment of molecules (degree of hydration and crystallinity, different isomers and polymorphic forms, long-chain polymers of different level of branches and saturations. 

In this presentation, two examples of the use of vibrational spectroscopy to probe water-solid interactions in materials of interest to the food and pharmaceutical sciences are described. First, the interaction of water vapor with hydrophilic amorphous polymers has been investigated. Second, water accessibility in hydrated crystalline versus amorphous sugars has been probed using deuterium exchange. In both of these studies, Raman spectroscopy was used as the method of choice. Raman spectroscopy is especially useful of these types of studies as it is possible to control the environment of the sample more easily than with infrared spectroscopy. 

An analogous situation has been observed in the case of the five polymorphs and the hydrate form of the 2-thiobarbituric acid (tba), which have been isolated and characterized by single-crystal X-ray diffraction and X-ray powder diffraction at variable temperature in combination with ID and 2D ( H, C, and N) solid-state NMR and Raman spectroscopy (Figure 3). In tba-II and in the hydrate, the tba molecules are present in their enol form, while only the keto isomer is present in crystalline tba-I, tba-III, tba-V, and tba-VI. On the other hand, a 50 50 ordered mixture... 

In situ thermal transitions were also described by Taylor et al., who examined the isothermal dehydration behavior of trehalose dihydrate [29]. For small particle size fractions (<45 fjLm), heating at 80°C caused loss of peak definition until, at 210 min, amorphous material was present. In contrast, a larger particle size fraction (>425 fim) converted to the crystalline anhydrous form of the material. The kinetics of this conversion was probed from the Raman data using peak height ratios with time a two-stage rearrangement was indicated. A broader consideration of pharmaceutical hydrates, including their characterization by several techniques (NMR, Raman spectroscopy, and isothermal calorimetry) can be found in the literature [30] as can a review of the use of spectroscopic techniques for the characterization of polymorphs and hydrates [31]. 

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