Solid-state analysis pharmaceutical

R. Vehring, Red-excitation dispersive Raman spectroscopy is a snitable techniqne for solid-state analysis of respirable pharmaceutical powders, Appl. Spectrosc., 59, 286-292 (2005). 

Brittain, H. G. Solid-State Analysis, Chapter 3. In Handbook of Modern Pharmaceutical Analysis (S. Ahuja and Scypinski, S., Eds.), pp. 57-84. Marcel Dekker, New York, 2001. 

Newman AW, Bym SR. Solid-state analysis of the active pharmaceutical ingredient in drug products. Drug Discov Today 2003, 1 Oct 8(19) 898-905. 

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]. 

UV-Vis spectroscopy in solution is probably one of the most frequently applied spectroscopic methods in the quantitative analysis of pharmaceuticals (see other chapters of this book). In solid-state analysis, this situation is quite the opposite since most solids are too opaque to permit the use of this technique in the conventional transmission mode. UV-Vis spectroscopy on solids can only be realized via diffuse-reflection techniques connected with mathematical corrections (e.g. Kubelka-Munk function) and lacking the high reproducibility of UV-Vis spectroscopy in solution owing to particle dispersion effects. The number of published papers on the application of UV-Vis spectroscopy to solid pharmaceuticals is very small and these papers include topics such as photo-stabihty of dyes and active ingredients in tablets, drug-excipient interactions in dmg products, quantitative measurements on discolouration in dmg products, and others. For further reading we refer to Brittain [26] and the literature cited therein. 

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 goal of early stage solid-state analysis is the determination of the tendency of a compound to crystallize into different forms. It may have many forms like sulfathiazole with at least four polymorphs [6] or methylestradiol with one anhydrous form, two hydrated forms and at least two solvated forms [4]. This information guides the course of the future studies. If only one pharmaceutically significant form exists, then the subsequent studies should be straightforward and relatively rapid. If many forms exist, choosing the optimal form for development may require extensive time and study. It is useful to operate on the principle that all organic compounds crystallize in different forms and that the only questions are How many and How important McCrone [7] put the matter this way ... 

I. Wawer, M. Piskiak, Z. Chilmonczyk, H, C, N NMR analysis of sildenafil base and citrate (Viagra) in solution, solid state and pharmaceutical dosage forms, J. Pharm. Biomed. Anal. 38 (5) (2005) 865-870. 

F. G. Vogt, A Multi-Disciplinary Approach to the Solid-State Analysis of Pharmaceuticals , Am. Pharm. Rev., 2008, 11, 50. 

Vibrational Spectroscopy [Infrared (mid-IR, NIR), Raman]. In contrast to X-ray powder diffraction, which probes the orderly arrangement of molecules in the crystal lattice, vibration spectroscopy probes differences in the influence of the solid state on the molecular spectroscopy. As a result, there is often a severe overlap of the majority of the spectra for different forms of the pharmaceutical. Sometimes complete resolution of the vibrational modes of a particular functional group suffices to differentiate the solid-state form and allows direct quantification. In other instances, particularly with near-infrared (NIR) spectroscopy, the overlap of spectral features results in the need to rely on more sophisticated approaches for quantification. Of the spectroscopic methods which have been shown to be useful for quantitative analysis, vibrational (mid-IR absorption, Raman scattering, and NIR) spectroscopy is perhaps the most amenable to routine, on-line, off-line, and quality-control quantitation. 

Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a powerful technique used in the analysis of solids, and is currently finding more and more applications, particularly in the analysis of pharmaceutical formulations. It is a non-destructive, non-invasive technique that can be employed to simultaneously examine the physical and chemical states of both the active pharmaceutical ingredient (API) and the excipients present as they exist within the formulation. It is also highly selective, as nuclei of the API often have different chemical shifts than do common excipients. 

Bugay, D.E. Solid-state nuclear magnetic resonance spectroscopy. Drugs Pharm. Sci. 2002,117,467-499. Handbook of Pharmaceutical Analysis. 

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