PhD defence P.H.M. (Pauline) Janssen

The role of excipients in pharmaceutical powder-to-tablet continuous manufacturing

The pharmaceutical industry is continuously looking for strategies and solutions that can improve quality and efficiency of manufacturing processes. As a result, there has been a significant shift towards continuous manufacturing (CM). Traditionally, tablets have been produced by batch processes, in which all ingredients are discharged in one unit operation. Production stops and material is removed after each processing step. In contrast, in a continuous process there are no discrete process steps and material is gradually moving through the different operating units. 

In spite of the increasing interest the pharmaceutical industry, CM is still new to many pharmaceutical companies. Much knowledge has been established on the role of raw material properties in batch processing, but this knowledge is not directly transferable to continuous processes. In order to enable the transition from batch production to continuous production, each processing step needs to be re-designed. The design of robust continuous processes requires a thorough understanding of the impact of material properties on each unit operation in a continuous manufacturing line. 

In this thesis, the role of excipients for continuous manufacturing of tablets is evaluated. Unit operations that are discussed include feeding, blending, dry granulation, lubricant blending, and die filling. Integrated continuous direct compression processes are also evaluated and compared to batch processing. Additionally, the impact of material properties on the disintegration performance of tablets are discussed. The thesis concludes with an expert opinion on existing gaps in the industry to optimize the use of excipients in continuous manufacturing processes.

Supervisor:        prof. dr. H.W. (Henderik Willem) Frijlink
Co-supervisor:  dr. W.L.J. (Wouter) Hinrichs