Pharmaceutical solids characterization

Physical Characterization of Pharmaceutical Solids, edited by Harry G. Brittain... 

With these concerns in mind, it is appropriate to outline a comprehensive program for the physical characterization of pharmaceutical solids. A modem industry cannot tolerate the inconsistent practices of the past, where the only physical properties that might be documented were those that could be conveniently measured. It is of extreme importance that investigators measure the parameters that need to be measured and not merely collect the type of data that is convenient to obtain. Proper physical characterization must be systematic in its approach, and it should follow a protocol that is rationally designed to obtain all needed information. 

A systematic approach to the physical characterization of pharmaceutical solids has been outlined [6], and it will be filled out in significantly more depth in the chapters of the present work. Within this system, physical properties are classified as being associated with the molecular level (those associated with individual molecules), the particulate level (those pertaining to individual solid particles), or the bulk level (those associated with an assembly of particulate species). 

Infrared (IR) spectroscopy, especially when measured by means of the Fourier transform method (FTIR), is another powerful technique for the physical characterization of pharmaceutical solids [17]. In the IR method, the vibrational modes of a molecule are used to deduce structural information. When studied in the solid, these same vibrations normally are affected by the nature of the structural details of the analyte, thus yielding information useful to the formulation scientist. The FTIR spectra are often used to evaluate the type of polymorphism existing in a drug substance, and they can be very useful in studies of the water contained within a hydrate species. With modem instrumentation, it is straightforward to obtain FTIR spectra of micrometer-sized particles through the use of a microscope fitted with suitable optics. 

An initial use of reflectance spectroscopy in the characterization of pharmaceutical solids concerned studies of the stability of coloring agents in tablet formulations. With the description of a device that enabled the surface of intact tablets to be studied [14], the photostability of various dyes and lakes in tablets was followed [15,16]. Exposure of formulations to both normal and exaggerated light conditions was investigated, and the kinetics of the photodegradation evaluated. In most cases, the photoreactions appeared to follow first-order kinetics. 

Although UV/VIS diffuse reflectance spectroscopy has not been used extensively in the study of pharmaceutical solids, its applications have been sufficiently numerous that the power of the technique is evident. The full reflectance spectra, or the derived colorimetry parameters, can be very useful in the study of solids that are characterized by color detectable by the human eye. It is evident that questions pertaining to the colorants used for identification purposes in tablet formulations can be fully answered through the use of appropriately designed diffuse reflectance spectral experiments. With the advent of newer, computer-controlled instrumentation, the utility of UV/VIS diffuse reflectance as a characterization tool for solids of pharmaceutical interest should continue to be amply demonstrated. 

The topics of polymorphism and pseudopolymorphism dominate the majority of publications that deal with utilizing infrared spectroscopy for the physical characterization of pharmaceutical solids. Typically, in each of the publications, IR spectroscopy is only one technique used to characterize the various physical forms. It is important to realize that a multidisciplinary approach must be taken for the complete physical characterization of a pharmaceutical solid. Besides polymorphism, mid- and near-IR have been utilized for identity testing at the bulk and formulated product level, contaminant analysis, and drug-excipient interactions. A number of these applications will be highlighted within the next few sections. 

Clearly, the potential applications for vibrational spectroscopy techniques in the pharmaceutical sciences are broad, particularly with the advent of Fourier transform instrumentation at competitive prices. Numerous sampling accessories are currently available for IR and Raman analysis of virtually any type of sample. In addition, new sampling devices are rapidly being developed for at-line and on-line applications. In conjunction with the numerous other physical analytical techniques presented within this volume, the physical characterization of a pharmaceutical solid is not complete without vibrational analysis. 

Within various pharmaceutical laboratories (industrial and academic), the mul-tinuclear technique of solid state NMR has primarily been applied to the study of polymorphism at the qualitative and quantitative levels. Although the technique ideally lends itself to the structure determination of drug compounds in the solid state, it is anticipated that in the future, solid state NMR will become routinely used for method development and problem solving activities in the analytical/materials science/physical pharmacy area of the pharmaceutical sciences. During the past few years, an increasing number of publications have emerged in which solid state NMR has become an invaluable technique. With the continuing development of solid state NMR pulse sequences and hardware improvements (increased sensitivity), solid state NMR will provide a wealth of information for the physical characterization of pharmaceutical solids. 

Methods for the determination of solubility have been thoroughly reviewed [21,22], Solubility is normally highly dependent on temperature, and so the temperature must be recorded for each solubility measurement. Plots of solubility against temperature, as exemplified by Fig. 4 [23,24], are commonly used for characterizing pharmaceutical solids and have been extensively discussed [1,24]. Frequently (especially over a relatively narrow temperature range), a linear relationship may be given either by a van t Hoff plot according to [23]... 

With over 1300 bibliographic citation, figures, tables, and equations. Physical Characterization of Pharmaceutical Solids is an incomparable resource for industrial and product development pharmacists and pharmaceutical scientist spectrosoopials physical, surface, and colloid chemists and upper-level undergraduate and graduate students in these disciplines. 

Physical characterization of pharmaceutical solids / eEHdd BjHIMfry31 G. Brittain. 

H.G. Brittain, Methods for the characterization of polymorphs and solvates. In H.G. Brittain (Ed.), Polymorphism in Pharmaceutical Solids, Marcel Dekker, New York, 1999, pp. 227-278 Chapter 6. 

Pharmaceutical solids can generally be described as crystalline or amorphous (or glassy). In fact, the actual solid phase composition of a pharmaceutical formulation is usually characterized by an intermediate composition, both crystalline and amorphous in character. In a multicomponent system, such as a solid formulation comprising drug and excipient(s), certain components or even a single component may be... 

J.M. Chalmers and G. Dent, Vibrational spectroscopic methods in pharmaceutical solid-state characterization. Polymorphism, 95-138 (2006). 

Yu L. Amorphous pharmaceutical solids preparation, characterization and stabilization. Adv Drug Deliv Rev 2001 48 27-42. 

Brittain H. Methods for the characterization of polymorphs and Solvates in Pol5unorphism in Pharmaceutical Solids. In Brittain H, ed. 1st ed. New York Marcel Dekker Inc., 1999 227-278. 

Roggo, Y., Jent, N., Edmond, A., Chalus, P., and Ulmschneider, M. (2005b), Characterizing process effects on pharmaceutical solid forms using near-infrared spectroscopy and infrared imaging, Fur. J. Pharm. Biopharm., 61(1-2), 100-110. 

Pharmaceutical Excipients Characterization by IR, Raman, and NMR Spectroscopy, David E. Bugay and 14/ Paul Findlay Polymorphism in Pharmaceutical Solids, edited by Harry G. Brittain Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products, edited by Louis Rey and Joan C. May... 

Byrn et al. (1995) have offered strategic approaches for characterizing pharmaceutical solids with speciLc emphasis on regulatory considerations. The International Conference on Harmonisation (2000) and the FDA (2004) have also presented their guidance for industry on how to address the issues of pharmaceutical polymorphism. In general, the information that is useful at the early development phase includes... 

Brittain HG, Bogdanowich SJ, Bugay DE, DeVincentis J, Lewen G, Newman AW. Physical characterization of pharmaceutical solids. Pharm Res 1991 8(8) 963-973. 

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