Solid-state properties study methods

The solid-state properties like crystallinity, polymorphism (crystal structure), shape (morphology), and particle size of drugs are important in the stability, dissolution, and processibility of drugs. Some commonly used methods in solid-state studies include microscopy, hot stage microscopy with polarized light, x-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared FTIR/Raman, and solid-state NMR. 

Polymorphism can influence every aspect of the solid state properties of a drug. Many of the examples given in preceding chapters on the preparation of different crystal modifications, on analytical methods to determine the existence of polymorphs and to characterize them and to study structure/property relations, were taken from the pharmaceutical industry, in part because there is a vast and growing body of literature to provide examples. One of the important aspects of polymorphism in pharmaceuticals is the possibility of interconversion among polymorphic forms, whether by design or happenstance. This topic has also been recently reviewed (Byrn et al. 1999, especially Chapter 13) and will not be covered here. Rather, in this section, we will present some additional examples of the variation of properties relevant to the use, efficacy, stability, etc. of pharmaceutically important compounds that have been shown to vary among different crystal modifications. 

Advances in techniques include sophisticated NMR methods, both in solution and the solid-state, and computational methods, and these, coupled with X-ray diffraction and other established methods, have been applied to the study of a wide variety of structures. Topics covered in the book include Sn(II) clusters, tin Zintl ions, Sn(II) heterobimetallic compounds, RsSn+ cations, stannylenes (R2Sn ), stannenes (R2Sn=SnR2 and R2Sn=CR2), stannynes (RSn=SnR), organotin oxide, carboxylate and sulfonate clusters, dendrimers and macrocycles, organotin polymers, Sh-tt interactions, unusual bondings and structures, and compounds with non-linear optical properties. 

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. 

This is one of the most frequently used methods to study solid-state properties. The flux t5q)e DSC involves heating the sample and reference samples at a constant rate using thermocouples, to determine how much heat is flowing into each sample and thus finding the differences between the two. Examples of such DSC instrumentation are those provided by Mettler and duPont. The power compensation DSC (e.g., Perkin-Elmer), an exothermic or endothermic event, occurs when a sample is heated, and the power added or subtracted to one or both of the furnaces... 

These simulation studies, based on either static lattice, MD or ab initio methods, have been able to provide deeper insight as to the fundamental solid state properties at the atomic level, particularly in the following key areas (a) defect chemistry and dopant-vacancy association, (b) mechanisms of oxygen ion migration, (c) structures and stability of surfaces (mainly (110) and (111)), (d) energetics of redox reactions... 

Nanocrystal and cluster science is the study of the chemical synthesis and physical properties of individual nanocrystals and nanotubes. It seeks to understand the evolution of molecular properties into solid state properties with increasing size. Methods include so-called bottom-up chemical synthesis of nanocrystals, nanowires, and very large species, as well as physical molecular beam approaches. Advanced physical characterization of single nano-objects by local probe methods and optics is critical here. The area is intrinsically interdisciplinary at the junction of physics, chemistry, and materials science. Outstanding chemical research in nanocrystal science is often found in a wide variety of science and engineering departments. 

All the solid-state properties of the various polymorphic modifications of a compound are different, but the difference is only marginal in nature, sometimes beyond the limit of detection of a particular analytical method. Therefore, to avoid erroneous conclusions it is important to look at potential polymorphic systems using a variety of analytical techniques. " By relying on too few analytical techniques, one may fail to discover a polymorph. It may require substantial effort for complete elucidation of substances with multiple polymorphic forms, especially when previous studies have characterized the forms inadequately. 

Optimization of the electrodes for these fuel cell systems has just started. Work has been done on the optimization of electrode structure for operation under hot, dry conditions, but less has been done to study catalysis under these conditions. Part of the reason for this is that as stated above there are no commercially available polymeric materials available for the development of new electrodes studies. It is hoped that until commercially available materials for this application become available that researchers offer to share their materials. This will, however, be insufficient as the ionomers developed for catalyst layers need different properties than ionomers developed to act as fuel cell membranes. The other major issue is that catalysts for fuel cells mn under conditions of water saturation have been developed using liquid phase electrochemical methods. It will be extremely important that new catalyst for fuel cells to be operated under hot, dry conditions be developed by solid-state electrochemistry. New methods must also be developed so that electrodes containing compatible ionomers can be tested. 

NMR spectroscopy is a well-established analytical technique in biofuel research. Over the past few decades, lignocellulosic biomass and its conversion to supplement or displace non-renewable feedstocks has attracted increasing interest. The application of solid-state NMR spectroscopy has long been seen as an important tool in the study of cellulose and lignocellulose structure, biosynthesis, and deconstruction, especially considering the limited number of effective solvent systems and the significance of plant cell wall three-dimensional microstructure and component interaction to conversion yield and rate profiles. The article by Foston reviews common and recent applications of solid-state NMR spectroscopy methods that provide insight into the structural and dynamic processes of cellulose that control bulk properties and biofuel conversion. 

Chapter 2 we worked through the two most commonly used quantum mechanical models r performing calculations on ground-state organic -like molecules, the ab initio and semi-ipirical approaches. We also considered some of the properties that can be calculated ing these techniques. In this chapter we will consider various advanced features of the ab Itio approach and also examine the use of density functional methods. Finally, we will amine the important topic of how quantum mechanics can be used to study the solid state. 

As noted before, thin film lubrication (TFL) is a transition lubrication state between the elastohydrodynamic lubrication (EHL) and the boundary lubrication (BL). It is widely accepted that in addition to piezo-viscous effect and solid elastic deformation, EHL is featured with viscous fluid films and it is based upon a continuum mechanism. Boundary lubrication, however, featured with adsorption films, is either due to physisorption or chemisorption, and it is based on surface physical/chemical properties [14]. It will be of great importance to bridge the gap between EHL and BL regarding the work mechanism and study methods, by considering TFL as a specihc lubrication state. In TFL modeling, the microstructure of the fluids and the surface effects are two major factors to be taken into consideration. 

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