(201e) The Development of Continuous Table Manufacturing Process Using Roller Compaction

Solid dosage forms, such as tablets and capsules, have been predominately manufactured through batch processes in pharmaceutical industry for years. The development of continuous manufacturing process is a current emerging demand in pharmaceutical industry to reduce the huge costs associated with process scale-up. To demonstrate the feasibility of continuous manufacturing tablets, a test bed with sequential blending, dry-granulating, lubricating, and tableting of dry powders and granules is under development at Purdue. This test bed will be used as the platform to understand the science behind the process, to build predictive models for process design and online process control strategies, and to optimize the manufacturing process in a closed loop.

Our specific interest is in the manufacture of ribbons with high API loading. As the first stage of development, a highly efficient, small scale continuous mixer (2 Kg) (continuously loaded using two loss-in-weight feeders) and a roller compactor have already been set up for continuous ribbon production. The model API, acetaminophen (APAP), and excipients, including microcrystalline cellulose (MCC), magnesium stearate (MgSt) and Cal-O-Sil® (SiO2) are selected as the model system to study the performance of the manufacturing process. The tuneup of process operating parameters was started with the formulation of APAP/MCC ratio as 50/50. The operating parameters include APAP and MCC feeding rates, paddle mixing rate, roll pressure, roll speed and roll gap. Then variety formulations containing 40-60% acetaminophen with different levels of lubricants were tested to prepare ribbons with desirable densities for future milling to prepare dry granules for further tableting.

In this work, we show the results of various experiments to characterize material properties, equipment performance, and control system performance including the effect of the API:excipient ratio, overall API and excipient throughput, and equipment settings on the blender and the roller compactor. We offer some general conclusions about how the experimental results can be used and extended.