(465a) Continuous Operations in Pharmaceutical Solid Dosage Form Manufacturing: Dry Granulation Case Study

In recent years, pharmaceutical manufacturing has experienced pressure to change in three interrelated directions. Due to changing market conditions, there is a desire to shift to real-time release (RTR) of drug products to the market soon after manufacturing. The paradigm shift towards RTR requires the implementation of Quality-by-Design (QbD), to obtain a fundamental understanding of the effect of formulation and process variables on the drug product quality attributes, as well as the scientific basis for developing control strategies for the process. The use of process analyzers is another critical component of the QbD framework , for close monitoring of critical process and product parameters and providing the necessary information for use in process control.

In this work, we present a case study in building and operating a continuous dry granulation manufacturing line for production of pharmaceutical tablets at Purdue University as part of the Engineering Research Center for Structured Organic Particulate Systems. We describe the individual powder-handling unit operations: feeding powders, continuous blending, roller compaction, ribbon milling, granule lubrication, tableting. We describe the process data collected using online sensors: NIR, microwave, and X-ray instruments, developed in-house or purchased off the shelf. We describe the automation and process management system: standard DCS features in DeltaV, and custom code developed in-house. We describe our operational procedures developed from both theory and experience. Finally we describe research activities that have been supported by the dry granulation test bed, and how the collected process information is used to improve the manufacturing process.