(342f) "Correlating Raw Material Properties to Critical Processing Parameters to Critical Quality Attributes in a Direct Compaction Continuous Line."

Callegari, G., Rutgers University
Muzzio, F., Rutgers University
O'Connor, T., U.S. Food and Drug Administration
In the last few years, Pharmaceutical manufacturing is experiencing unprecedented scientific and technological innovation as it has been involved in a fundamental transformation from batch to continuous. This revolution has the potential of reducing both the manufacturing time and cost, increase process control and improve overall process quality.

This study demonstrates a systematic methodology to find the critical processing parameters affecting the critical quality attributes of tablets produced in the continuous direct compaction manufacturing line. The methodology is demonstrated in a case study where the API is fixed, the formulation is varied along the DOE but keeping the API at low concentrations (2 to 10%).

The approach follows a screening bi-block two level fractional factorial DOE to elucidate the critical process parameters and corresponding failure modes of the continuous line which depends on the material properties of the formulation. The screening study involves eight processing and two formulation parameters but it only consists on twenty four experiments. A three level factorial DOE on the remaining parameters is then run for characterization and optimization purpose with the ultimate goal to relate material properties to the critical processing parameters and finally to the critical quality attributes of the tablets produced.

The study is run in Rutgerâ??s direct compaction continuous line and consists of two feeders (API and excipient) connected to a mill and to a blender with a third feeder (lubricant) connected also to the blender, bypassing the mill to prevent blendâ??s over lubrication. After the blender, the mix flows through a chute to the feed frame of the rotary tablet press where tablets are compacted. The quality attributes measured on tablets are content uniformity, weight variability, dissolution and hardness, but only the first is expected to have a relevance in this case study at low API concentration (2 to 10%).