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Coating thickness and spatial uniformity. CT enables you to measure the thickness and the uniformity of coatings applied to tablets and capsules, and because it can segment those measurements from the substrate, you can analyze the coating independent of the product's internal structure. Software tools also allow you to specify minimum and max- imum thickness criteria and automatically report both in a spreadsheet format. Furthermore, the data can be displayed in 3D, with the thicknesses spatially color-coded within the product image (Figure 4). It's even possible to evaluate products with more than one coating layer, enabling you to see thickness anomalies, gaps between layers, and inclu- sions and voids within or between the layers (Figure 5). Product development. Developing a new drug prod- uct—and often a new process to go with it—may require theoretical modeling, followed by manufacturing some samples. You then test those samples to see how they jibe with the models. If you use traditional equipment, many of the samples will be destroyed. CT, however, can reduce and sometimes eliminate the need for destructive testing, and the data you obtain can be used to fine-tune the manufac- turing process. That's possible because just one CT scan of a tablet can produce the equivalent of thousands of the cross-sections that would be obtained using destructive means. These virtual slices through multiple planes within the product's CT volume enable you to identify and define process variability faster. That, in turn, enables you to refine the model or the process itself to obtain the critical quality attributes the product requires. CT processes specimens so quickly that some types of data are available in minutes or even seconds. Variability in composition and density. Depending on how a tablet granulation is prepared, how it performs on the tablet press, and other factors, particles of the API(s) and excipients may segregate due to differences in density, size, shape, or other characteristics. That becomes a prob- lem when how uniformly the API is distributed within the tablet corresponds to its efficacy. It may even be a critical quality attribute—particularly in multiparticulate, modified- release, and multilayer tablets. With CT, you can visualize the distribution of the ingredients in the final dosage form and use the information to adjust the formulation and/or process. Evaluating how well a granulation process prevents powder segregation is one example. By spatially mapping the API or the excipient, CT can reveal how changing dif- ferent variables affects the final product (Figure 6). Impurities and foreign material. Even with tight con- trols, there is always the potential for impurities or foreign materials to taint the product. If that happens and the for- eign material varies in density, shape, or size from that of the baseline formulation, CT can often detect it (Figure 7). CT can even characterize the foreign material if a database of material standards is accessible. Intellectual property. Thousands of patents address the physical makeup of tablets and capsules in terms of coat- ings, excipients, shape, and manufacturing processes. With CT, you can add precision to patent applications that define the physical form of a product. Additionally, CT provides exceedingly fine detail that helps you compare products during intellectual property investigations. Performance correlation. When we "pop a pill" we obvi- ously expect it to perform as intended. In some cases, it relieves a painful symptom, and other times it keeps us alive. Whatever the case, we expect that tablet or capsule to work the same every time, within the same time frame, and at the same potency. In fact, some people's careers are dedi- cated to ensuring the uniform, consistent function of drug products. CT can help meet that goal—in tandem with existing techniques—by providing a more complete refer- ence point for performance-correlation studies. The CT- derived data can then be used to establish more compre- hensive product-screening standards. Figure 6 Spatial mapping of a capsule product's constituents Figure 4 Spatial color coding of capsule wall thickness Figure 5 CT scans of coated tablets can measure wall thickness and reveal thickness anomalies, gaps between multiple layers, and inclusions and voids. Tablets & Capsules January 2016 17