Top spray granulation is a widely used technique in the pharmaceutical industry for creating granules from damp, powdered substances in fluid bed dryers. It is crucial to maintain residual moisture within defined parameters to prevent particle breakage or clumping (stickiness) of the bulk material. Near-infrared spectroscopy (NIRS) enables real-time monitoring of residual moisture levels in powders post-drying.

This Process Application Note provides a detailed account of the inline assessment of moisture during a pilot scale granulation process using a 2060 The NIR Analyzer from Metrohm Process Analytics. The 2060 The NIR Analyzer delivers rapid, reagent-free, and nondestructive analysis of residual moisture in powders, facilitated by a fluid bed probe specially tailored for such applications.

During top spray granulation, powder is fluidized in a fluid bed dryer and a liquid binder solution is sprayed onto the product. After spraying the liquid into the formulation and forming the granule, the product must be dried to the proper moisture level.

If the granules are over-dried, movement in the fluid bed can cause their fracture (creating undesirable fine particles) and can damage the formulation due to hydration changes in some active ingredients and excipients. If the granules contain too much residual moisture, the product will not flow properly and may clump together. This can cause problems with subsequent processing, including a sticky product and product instability during storage.

Samples are typically withdrawn from the fluid bed with a sample thief during processing and then analyzed offline for moisture content in a laboratory. This delay before the analysis results are available to the operator can cause critical processing decisions (e.g., determining when the drying process should end) to be made without optimal product moisture information. Top spray granulation completion is often based on time or product temperature—not moisture content.

The drying process in a fluid bed dryer can be quickly monitored inline using near-infrared spectroscopy (NIRS) technology. NIRS can help operators to determine the residual moisture level for better process understanding, control, and end of drying process determination. Figure 1b shows a trend chart of the moisture content determined by NIRS versus time.

A fluid bed probe specifically designed for these applications is used with a «spoon» and purge vents located on the probe tip (Figure 1a). After each NIR <spectrum is collected, an air purge exiting through the ports in the probe clears the «spoon» for a new sample.

A reference method must still be in use. An appropriate range of samples covering the process variability should be analyzed by both methods to build an accurate NIRS model.

Correlations are made to process specifications. The correct NIRS probe must be placed in-situ in a manner that provides sufficient sample contact with the probe tip window. Correct probe design and proper placement in process equipment is of high importance.