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Visualization and analysis of pharmaceutical solids by X-ray microscopy

Winter 2014 Volume 30, No. 1
Yoshihiro Takeda and Kensaku Hamada

A current trend in drug delivery systems is the use of multicoated or orodispersible tablets. These new systems increase bioavailability and can improve patient compliance by removing the need to swallow. The functionality of these structured tablets is sensitive to fluctuations in the manufacturing process. The chemical formulation is important, but now the physical properties of the active ingredients and other compounds in the tablet have become important for the development, design, process optimization and quality control.

A prospective technique for the visualization and analysis of the 3-dimensional structure of pharmaceutical solids is sub-micron X-ray microscopy. Pharmaceutical applications of this technique have been limited for two primary reasons. The first reason is that the penetrating power of the X-rays used by the conventional systems is too high for small organic samples composed of the light elements such as carbon, hydrogen, oxygen and nitrogen. The small size and elemental composition of these samples make them too “transparent” to the X-rays of conventional systems, and thus limits the application areas of the existing technology to heavier samples such as electronics devices (silicon, gallium arsenide) or bones (calcium and phosphorus). The second reason is that pharmaceutical applications require both high resolution and a wide field of view, concurrently. Specifically, a resolution of a few microns is needed over the whole tablet, several millimeters, to evaluate granule deformation or micro-cracks caused by compaction during tableting. Until now, it has been difficult to satisfy these two conflicting requirements by X-ray analysis.

In order to make high resolution, large field of view measurements possible, Rigaku has developed the nano3DX, a novel X-ray microscope capable of analyzing the sub-micron structures of granules and tablets. This article reports the result of the measurements on several over-the-counter (OTC) tablets to evaluate the effectiveness of the system for pharmaceutical applications.


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