Use of the near-infrared reflectance method for measurement of moisture content during granulation.

The purpose of this study was to demonstrate the use of a near-infrared (NIR) method for in-process control of a placebo formulation. An NIR setup with a multichannel detector was applied in the measurement of water during fluidized bed granulation. The effects of two critical granulation parameters were studied using the central composite design. The present NIR setup with three wavelengths proved applicable for in-line moisture measurement. The 1990 nm signal was used for measurement of water and the 1745 and 2145 nm signals were used to correct the change in spectra baseline during granulation. Variations in inlet air conditions proved to be critical factors, explaining differences in the granule size distributions. Differences in granule moistening and drying rates resulting from varying inlet air conditions could be measured with the NIR setup. The moisture content of granules at the end of the spraying phase explained part of the differences in granule size distributions. The moisture content of granules at the end of the drying phase affected the tableting behavior of granules. The results suggested that direct measurement of granule moisture content facilitates the in-process control of the granulation.