Real-Time In-Line Monitoring of the Impact of Process Parameter Changes on Critical Quality Attributes in Fluid Bed Granulation using Process Analytical Technology 

The optimisation of a process to increase yield while reducing cost is a significant challenge. Understanding the manufacturing process is the key to identifying the critical processes parameters that affect process CQAs. To increase yield, manufacturers are attempting to decrease batch rejection and reduce waste. The US FDA recommends that by introducing Process Analytical Technologies (PAT) it will be possible to increase the consistency and quality of drug products and reduce production time and cost.

Critical Process Parameters (CPPs) within a manufacturing process are factors which contribute to the Critical to Quality Attributes (CQAs). A strategy to achieving increased yield is to use PAT to monitor the CPPs in-line in real-time to allow for control of the CQAs instead of testing end product to assess if it is of sufficient quality. End product testing will not allow for CPPs to be adjusted in-process and in turn this could result in batch rejection or increased wastage.

In granulation, both particle size distribution and moisture content are considered Critical Quality Attributes for the process and should be monitored. This study aims to determine, through in-line measurement, the effects of changing process parameters on the particle size profile and moisture content during a fluid bed granulation process.