(444a) QbD of Continuous Pharmaceutical Tablet Manufacturing

Koynov, A. A., Rutgers University
Vanarase, A. U., Rutgers University
Engisch, W. E. Jr., Rutgers University
Cuitino, A., Rutgers University
Muzzio, F. J., Rutgers University

The batch-oriented manufacturing mind-set prevalent in the pharmaceutical industry has logically extended to the initial instances of implementation of QbD. While bringing along significant improvements to the process design paradigm, such implementations still suffer from the fragmentation inherent to batch processing, with process design often not taking into account the effects of up-stream processes. This work will show the extension of the Quality by Design approach to a continuous set-up for the manufacturing of pharmaceutical tablets. The unit operations considered are continuous feeding, blending, dry granulation using roller compaction and milling, lubrication and tablet compaction. A mapping of the design space of the entire system will be presented. The critical process parameters be identified, along with the critical quality attributes, both at each processing step and for the final product. The major paths of down-stream attribute variability propagation will be traced and the optimal points for PAT implementation will be prescribed. The results will be used to lay the foundation for the development of consistent recipes for integrated continuous manufacturing system design.