Solid-state analysis thermal methods

Pure silica Beta has been crystallized from alkali-free hydrogel containing tetraethyl-ammonium hydroxide and fumed silica at 413 K by the conventional hydrothermal synthesis method. Characterization has been done by XRD, IR, SEM, solid-state NMR, thermal analysis eind N2 adsorption. The results show that a highly crystalline pure silica Beta is formed. Si MAS NMR reveals that the pure silica Beta has a small number of sites originating from structural defects and almost half of sites are silanol groups. Thermal analysis shows that pure silica Beta possesses nonequivalent sites that are siloxy groups counterbalanced by TEA cations. 

A detailed account of polymorphism and its relevance in the pharmaceutical industry is given elsewhere in this volume and in the literature [42,46,47]. This section will focus on the use of vibrational spectroscopy as a technique for solid-state analysis. However, it should be noted that these techniques must be used as an integral part of a multidisciplinary approach to solid-state characterisation since various physical analytical techniques offer complimentary information when compared to each other. The most suitable technique will depend on the compound, and the objectives and requirements of the analysis. Techniques commonly used in solid-state analysis include crystallographic methods (single crystal and powder diffraction), thermal methods (e.g. differential scanning calorimetry, thermogravimetry, solution calorimetry) and stmctural methods (IR, Raman and solid-state NMR spectroscopies). Comprehensive reviews on solid-state analysis using a wide variety of techniques are available in the literature [39,42,47-49]. 

X-ray diffraction methods (powder, single crystal) Spectroscopy (UV, IR, Raman, solid-state NMR) Thermal analysis, microcalorimetry, solubility determination, vapour pressure determination Moisture sorption Microscopy and micromeritics... 

When solids react, we would like to know at what temperature the solid state reaction takes place. If the solid decomposes to a different composition, or phase, we would like to have this knowledge so that we can predict and use that knowledge In preparation of desired materials. Sometimes, intermediate compounds form before the final phase. In this chapter, we will detail some of the measurements used to characterize the solid state and methods used to foUow solid state reactions. This will consist of various types of thermal analysis (TA), including differentlEd thermal analysis (DTA), thermogravimetric analysis (TGA) and measurements of optical properties. 

Complexes 75 are remarkably stable at room temperature in the solid state and, when heated, they start to decompose only at about 130 °C (Cr) or 145 °C (W). Such a thermal stability is undoubtedly associated with their strongly dipolar nature, in which six possible ylide-type resonance forms contribute to the bonding (Fig. 12). As expected, analysis of the electronic structure of complex [W (=C=C=C=C=C=C=C(NMe2)2 (CO)5] by DPT methods showed that the LUMO is mostly localized on the odd carbon atoms of the chain, whereas the HOMO is on the even carbons. In accord with these electronic features, it was found that [W =C=C=C=C=C=C=C(NMe2)21(00)5] readily adds dimethylamine across the 05=05 bond, to give the isolable alkenyl-pentatetraenylidene derivative [W =C=C=C=C=C(NMe2)CH=C(NMe2)21(00)5] [69, 70]. 

Modern instrumental methods of analysis have provided scientists with a wealth of information regarding the nature of the solid state and the reactivity of solids. Knowledge of the structure of solids and an ability to study thermal behavior are essential to an understanding of the behavior of high-energy materials. 

X-ray diffractometry is the most powerful method to determine atomic coordinates of molecules in the solid state. X-ray crystal structure analysis was, however, rarely applied in the early years of development of persistent, long-lived alkyl carbocations and studies were only performed to investigate structures of carbocations of aryl derivatives and aromatic systems.65 This is due to the low thermal stability of alkyl carbocations and to the difficulties in obtaining single crystals of carbocations suitable for analysis. Since then, however, methods and instrumentation have improved significantly and X-ray crystal structure analysis has become a powerful tool to solve structural problems of carbocations.65,66... 

Ionization Methods/Processes. The recent development of several new ionization methods in mass spectrometry has significantly improved the capability for the analysis of nonvolatile and thermally labile molecules [18-23]. Several of these methods (e.g., field desorption (FD), Californiun-252 plasma desorption (PD), fast heavy ion induced desorption (FHIID), laser-desorption (LD), SIMS, and fast atom bombardment (FAB) or liquid SIMS) desorb and ionize molecules directly from the solid state, thereby reducing the chance of thermal degradation. Although these methods employ fundamentally different excitation sources, similarities in their mass spectra, such as, the appearance of protonated, deprotonated, and/or cationized molecular ions, suggest a related ionization process. 

Polymorphism is customarily monitored by melting point or infrared spectral analysis. However, other methods, such as X-ray diffraction, thermal analytical, and solid-state Raman spectroscopy, also can be used. It is expected that the sponsor will conduct a diligent search by evaluating the drug substance recrystallized from various solvents with different properties. Either the basis for concluding that only one crystalline form exists, or comparative information regarding the respective solubilities, dissolution rates, and physical/chemical stability of each crystalline form should be provided. 

The subhalides of tellurium are an especially important class of solid state compounds, and they have been the subject of intensive studies, so that a rather complete picture of their chemistry and their properties has been obtained in recent years. Because of their high tellurium content they contain fragments of the homonuclear tellurium chains their modified tellurium structures are of great current interest with respect to possibly significant physical properties. Consequently, the results of various investigations on the synthesis of the compounds, on phase analysis by thermal methods, on crystal growth, on the structures, on spectroscopic, thermodynamic, optical, photoelectric, electrochemical properties have been reported in the last two decades. In a comprehensive review (237) all significant results are reported and discussed in detail so that the present chapter will be restricted to some selected and chemically important features. 

In general, the various experimental techniques differ in sensitivity, and therefore in usefulness, from one portion of the phase diagram to another. Thus, thermal analysis is the best method for determining the liquidus and solidus, including eutectic and peritectic horizontals, but it may fail to reveal the existence of eutectoid and peritectoid horizontals because of the sluggishness of some solid-state reactions or the small heat effects involved. Such features of the diagram are best determined by microscopic examination or x-ray diffraction, and the same applies to the determination of solvus (solid solubility) curves. 

The constitnents of binary phenol mixtnres can be identihed by differential thermal analysis of a sample to which any of the aroyl chlorides 184-186 has been added. The thermogram is compared with a bank of differential thermograms of phenols, binary phenol mixtures and binary phenol derivatives. Most snch systems show weU-resolved endotherms corresponding to the melting points of the phenols and their acylated derivatives. The method is proposed for rapid identification of phenols in the solid state . 

Comprehensive spectral analysis including solid state FTIR, solid state Raman, and solid state C NMR by Raghavan et al. (1993), resulted in the following conclusion, particularly from sohd state C NMR ... spectral characteristics of Form I were interpreted in terms of the presence of more than one orientation for the n-butyl side chain and the imidazole ring. In addition, the spectral characteristics of Form II were consistent with a large molecular motion of the n-butyl side chain. Although spectral differences were observed, no conclusions about relative thermodynamic stabihty could be or were made from the spectral data, leaving those conclusions to the more traditional methods of thermal analysis (DSC) and solubihty measurements. 

Examination of the residual solid from solubility samples is one of the most important but often overlooked steps in solubility determinations. Powder X-ray diffraction (PXRD) is the most reliable method to determine whether any solid state form change has occurred during equilibration. The sample should be studied both wet and dry to determine if any hydrate or solvate exists. Thermal analysis techniques such as differential scanning calorimetry (DSC) can also be used to identify any solid-state transformations, although they may not provide as definitive an answer as the PXRD method. Other methods useful in identifying any solid-state changes include microscopy, Raman and infrared spectroscopy, and solid-state NMR (Brittain, 1999). When changes in solid-state properties are identified in solubility studies, it is important to link the new properties to the properties of known crystal forms so the solubility result can be associated with the appropriate crystal form. 

Equipment for thermal analysis is used extensively for the preformulation study. As in the solid-state investigation, interest is focused not only on the chemical change but also on the physical change, which can be illustrated appropriately by thermometric methods. 

---