Characterization of solid dosage forms

Purity and potency are two of the metrics that pharmaceutical quality assurance (QA) departments emphasize to determine if a batch may be released. To do this they typically employ HPLC and/or mass spectrometry to determine gross composition, and to verify the absence of any contaminants. However, only a small subset of tablets in a batch is tested because the tests destroy the sample. While these methods offer some insight into sample consistency, they provide no information on the distribution of the components in an individual finished form. Dissolution testing is used to indicate the manner and 

However, spectroscopic techniques, although nondestructive, do not provide the spatial information that can be critical in solving performance issues, or in developing true product and process understanding. Only techniques that combine both spatial and chemical identification information provide a complete set of tools to determine both product and process understanding. 

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Examples of application in the characterization of solid dosage forms... 

Although most often connected with investigations of solid dosage forms, diffuse reflectance spectroscopy can also be used to characterize alternative formulations. Through the use of a special sample cell, the technique has been used to study the stability of emulsions [37]. In this work, it was found that information could be obtained that pointed toward subtle changes in the emulsion microenvironment. 

Process aids do not usually contribute to the performance of the dosage form in terms of quality or in vivo performance. Indeed, lubricants, because of their hydrophobic nature, can hinder disintegration and dissolution of solid dosage forms unless the level and mode of incorporation is carefully characterized and controlled. Thus, in addition to drug-excipient interactions, the potential for interexcipient competition and incompatibility must be considered and studied. 

Apart from food industry (see Chapter 8), NIR chemical imaging has so far primarily been applied to qualitative and quantitative product characterization in the pharmaceutical industry. The ability to visualize and assess the compositional heterogeneity and structure of the end products is extremely important for both the development and manufacture of solid dosage forms [20]. Hence, NIR chemical images have been used to determine authenticity, content uniformity, particle sizes and distribution of sample components, polymorph distributions, moisture content and location, contaminations, coating and layer thickness, as well as a host of other structural details [21-29]. 

It is evident even to the casual observer that the vast majority of pharmaceutical products are administered as solid dosage forms, which are in turn produced by the formulation and processing of powdered solids. All too often characterization of raw materials and products has centered on aspects of chemical purity, with only passing attention being given to the physical properties of the solids. However, every pharmaceutical scientist knows of at least one instance in which a crisis arose due to some variation in the physical properties of input materials, and in which better characterization would have prevented the problem. 

In the present work, such a systematic approach to the physical characterization of pharmaceutical solids is outlined. Techniques available for the study of physical properties are classified as being associated with the molecular level (properties associated with individual molecules), the particulate level (properties pertaining to individual solid particles), and the bulk level (properties associated with an ensemble of particulates). Acquisition of this range of physical information yields a total profile of the pharmaceutical solid in question, whether it is an active drug, an excipient, or a blend of these. The development of a total profile is a requirement for successful manufacture of any solid dosage form. 

Various techniques available for characterization of solid-state properties of raw materials and Ln-ished solid dispersions are presented in this section. In most cases, solid dispersions are process into Lnished dosage forms using conventional approaches such as tabletting, encapsulation, and < forth, and the characterization of such Lnished dosage formulations are not presented here. 

Senderoff RI, Mahjour M, Radebaugh, GW. 1992. Characterization of adsorption behaviour by solid dosage form excipients in formulation development. Int. J. Pharm. 83 65-72. 

The development of a pharmaceutical product can be a long, arduous and expensive process. For those that are marketed in solid dosage forms that process deals with many matters of solid state chemistry, among them the detection, characterization, and preparation of various modifications. We have attempted here to touch on many of those issues, and as noted at the beginning of the chapter, examples of these various aspects of polymorphism and their manifestations in the pharmaceutical industry may be found throughout this book. 

Reutzel-Edens, S.M. Bush, J.K. Solid-state NMR spectroscopy of smaU molecules from NMR crystallography to the characterization of solid oral dosage forms. Am. Pharm. Rev. 2002, 5 (2), 112-115. 

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