In the pharmaceutical sector, the fluid bed granulator/dryer is an integral point in the manufacture of powdered materials (active ingredients or excipients). Particle size can be affected by several factors, among them the moisture content of the product in the fluid bed dryer. If over-drying occurs, the granules can fracture, resulting in fine particles which can adversely affect the final formulation. Product that is left too moist at the end of the process can clump together and cause blockages in the flow, as well as causing other manufacturing problems. 

Moisture content of the powder is determined via slow offline laboratory techniques such as loss of weight (10–30 minutes), after physical removal from the process with a sample thief. This manual sampling results in a delay, which can cause problems whenever critical processing decisions must be made, such as endpoint determination. Monitoring the moisture content directly leads to a more informed operator.

Real-time analysis of the moisture content in powders can be performed inline via near-infrared spectroscopy (NIRS) technology, which fits well within the Process Analytical Technology (PAT) initiative as recommended by the FDA. The drying process can be monitored constantly without manual intervention, allowing for better process understanding, control and endpoint determination. Development of a calibration model which properly correlates NIRS results to a laboratory reference method is necessary first. A fluid bed “spoon” probe designed specifically for this purpose is inserted directly into the dryer, as seen in the diagram below. After each NIR spectrum is collected, an air purge exiting through the ports located in the probe tip clears the “spoon” for a new sample. Each scan takes 30 seconds, ensuring there is always an accurate snapshot of the drying process at any time.

Product release delays caused by waiting for laboratory results can be minimized or eliminated as endpoint determination can be made when the moisture level asymptotically approaches a lower limit during the drying cycle. The operator is aided in making the decision to end the drying operation before the product is damaged or degraded. Output from the process analyzer could be used by the fluid bed dryer’s programmable logic controller (PLC) or integrated into SIPAT (Siemens Industry Process Analytical Technology) for closed loop process control decisions. The reduction in reprocessing steps saves both time and money, and improvement in the product quality can lead to even higher profits.