Imaging of Compacted Tablets

The ATR-FT-IR method is particularly suitable for the spectroscopic analysis of pharmaceutical tablets, mainly due to the minimal sample preparation required and the possibility of obtaining quantitative chemical informahon from the sample. Such advantages are important with this type of sample, because it is difficult to microtome a tablet into the suitable thicknesses (usually 10 gm) that are often needed for transmission studies. The diffuse-reflechon technique is also often very 

The latter approach enables measurement of the compacted tablet during and after the process of compaction, and can be used to evaluate the effect of pressure on the distribution of the different components and the density of the tablet [60]. 

The in situ compaction study is only possible by using hard ATR crystals, due to the high compressive force used for tablet compaction. Consequently, diamond is the material of choice here, and use of the diamond ATR accessory to obtain ATR-FT-IR images of compacted tablets has been demonstrated previously [35]. ATR-FT-IR images of a model pharmaceutical formulation containing 

Figu re 10.9 Micro ATR-FT-IR images of a tablet showing the distribution of caffeine, starch and HPMC. 

The ATR FT-IR method is particularly suitable for the spectroscopic analysis of pharmaceutical tablets because of the minimal sample preparation required and the possibility to obtain quantitative chemical information from the sample. These 

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The imaging data were collected over the spectral range of 1200-2400 nm at 10-nm increments using a Sapphire NIR-CI system (Spectral Dimensions, Inc., Olney, MD, USA). The size of FOV was 13 x 10 mm, each pixel sampling an area of approximately 40 x 40 pm. The concentrations of the active ingredients as reported from the manufacturer s label are 37% acetaminophen, 37% aspirin, and 10% caffeine. The remainder of the tablet mass represents the excipient (binder, disintegrant, and lubricant) materials. Pure acetaminophen, aspirin, and caffeine samples are obtained in either tablet form or powder compact and are used to obtain reference spectra of pure components. 

Figure 10.10 Schematic diagram showing the idea of in situ imaging of tablet compaction using a diamond ATR accessory.

The micro-ATR FT-IR imaging approach is readily applicable to study compacted tablets. The contact area of the ATR crystal is circular with a diameter in the region of 100 pm. This area is small enough to easily establish a homogeneous and intimate contact between the ATR crystal and the tablet. To prove this concept, a model tablet, composed of about 3 wt% caffeine in a matrix of starch HPMC of 4 6, was compacted and imaged using the micro-ATR method and the result is shown in Figure 9.10. 

Wray, P. et al. (2008) Compaction of pharmaceutical tablets with different polymer matrices studied by FTIR imaging and X-ray microtoraography. J. Pharm. Sci., 97 (10), 4269-4277. 

Our group was the first to report imaging with a diamond ATR accessory that provided a field of view of ca. 1 mm2 and the spatial resolution of ca. 15 pm without the use of an infrared microscope [18], The demonstration of the applicability of a diamond ATR accessory for FTIR imaging opened up a range of new opportunities in polymer research, from compaction of tablets [21-23] to studying phase separation in polymer blends subjected to supercritical fluids [24], This imaging approach was successfully utilised for the study of dissolution of tablets in aqueous solutions [25], We have also demonstrated macro... 

Elkhider N, Chan KLA, Kazarian SG. Effect of moisture and pressure on tablet compaction studied with FTIR spectroscopic imaging. J Pharm Sci 2007 96(2) 351-360. 

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