Solid-state analysis microscopy

The practical applications of the various microscopical techniques have created opportunities for microscopists in industry and, in particular, within pharmaceutical research and development. Microscopy is used extensively, from the earliest stages of drug discovery into late development and even into manufacturing. Pharmaceutical microscopy can be conveniently divided into physico-chemical and biological applications. This chapter will consider exclusively the physico-chemical aspects of microscopy in the pharmaceutical industry. There are three broad areas in which microscopy can play an important role in the development of drugs solid-state analysis, particle size and morphology studies, and contaminant identification. This chapter presents an overview of how microscopy contributes to each of these three areas. The emphasis will be on practical examples taken from the literature and from the author s experience. 

The objective of late stage solid-state analysis is to provide data for the choice of form for development. Microscopy has much to contribute to this analysis but generally plays an adjunct role to other techniques. Microscopy can, however, play a crucial role in some of the thermodynamic investigations leading... 

The use of solid state NMR for the investigation of polymorphism is easily understood based on the following model. If a compound exists in two, true polymorphic forms, labeled as A and B, each crystalline form is conformationally different. This means for instance, that a carbon nucleus in form A may be situated in a slightly different molecular geometry compared with the same carbon nucleus in form B. Although the connectivity of the carbon nucleus is the same in each form, the local environment may be different. Since the local environment may be different, this leads to a different chemical shift interaction for each carbon, and ultimately, a different isotropic chemical shift for the same carbon atom in the two different polymorphic forms. If one is able to obtain pure material for the two forms, analysis and spectral assignment of the solid state NMR spectra of the two forms can lead to the origin of the conformational differences in the two polymorphs. Solid state NMR is thus an important tool in conjunction with thermal analysis, optical microscopy, infrared (IR) spectroscopy, and powder... 

Direct analysis 7.1 XRD, XRF, infrared spectroscopy (NIR and MIR), solid-state nuclear magnetic resonance (NMR), advanced spectroscopy using synchrotron radiation, neutron activation, fluorescence, and visible and electron microscopy... 

Feltz, A. Martin, A. (1987) Solid-state reactivity and mechanisms in oxide systems. 11 Inhibition of zinc ferrite formation in zinc oxide - a-iron(lll) oxide mixtures with a large excess of a-iron(lll) oxide. In Schwab, G.M. (ed.) Reactivity of solids. Elsevier, 2 307—313 Fendorf, S. Fendorf, M. (1996) Sorption mechanisms of lanthanum on oxide minerals. Clays Clay Miner. 44 220-227 Fendorf, S.E. Sparks, D.L. (1996) X-ray absorption fine structure spectroscopy. In Methods of Soil Analysis. Part 3 Chemical Methods. Soil Sd. Soc. Am., 377-416 Fendorf, S.E. Eick, M.J. Grossl, P. Sparks, D.L. (1997) Arsenate and chromate retention mechanisms on goethite. 1. Surface structure. Environ. Sci. Techn. 31 315-320 Fendorf, S.E. Li,V. Gunter, M.E. (1996) Micromorphologies and stabilities of chromiu-m(III) surface precipitates elucidated by scanning force microscopy. Soil Sci. Soc. Am. J. 60 99-106... 

Tsukahara, Y., Nakaso, N., Ohira, K and Yanaka, M. (1996). Interaction of acoustic waves with solid surfaces. In Advances in acoustic microscopy, Vol. 2 (ed. G. A. D. Briggs and W. Arnold), pp. 103-65. Plenum Press, New York. [91, 149, 218, 226] Vetters, H Matthaei, A., Schulz, A., and Mayr, P. (1989). Scanning acoustic microprobe analysis for testing solid state materials. Mater. Sci. Engng. A122, 9-14. [199, 207,219]... 

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. 

Spectroscopic methods are nondestructive and can be used in conjunction with other solid-state techniques (TGA, microscopy, DSC, XRD) for the quantitative analysis of... 

It is evident from the above discussion that catalyst characterization is an activity important for scientific understanding, design, and troubleshooting of catalyzed processes. There is no universal recipe as to which characterization methods are more expedient than others. In the opinion of the writer, we will see continued good use of diffraction methods and electron microscopy, surface analysis, IR spectroscopy, and chemisorption methods, increased use of combined EM and ESCA analyses for determining the dopant dispersion, increased use of MAS-NMR and Raman spectroscopies for understanding of solid state chemistry of catalysts, and perhaps an increased use of methods that probe into the electronic structure of catalysts, including theory. 

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