Monitoring of API particle size during solid dosage form manufacturing process by chemical imaging and particle...

Agglomeration of API during a solid dosage form manufacturing process is followed from the bulk API, through the initial blend with the excipients to the ribbons by a combination of chemical imaging and particle sizing experiments. Particle size of the ingoing API was characterized using a Sympatec HELOS laser diffractometer. Chemical images of the API were obtained from the blends, granules, and ribbons using near-infrared (NIR) and Raman mapping instruments. All the chemical images are obtained in the univariate fashion through the API-characteristic wavenumbers. Light microscopy and laser diffraction were used to assess presence of large agglomerates in the bulk API. NIR chemical images of the sparsely distributed blend particles confirmed that the large agglomerates were not dispersed during the blending. Also, it was found that normal microscopy may be efficient at detecting those API agglomerates due to their distinct appearance (whiteness and size). The agglomerates were not detected in the NIR chemical images of the granules and the ribbons. This was more reliably confirmed by Raman chemical images in which small API domains were clearly identified which was not attainable by NIR mapping.