(451h) Product Robustness within a Dry Granulation Continuous Manufacturing Line

Authors: 
Dale, S., Vertex Pharmaceuticals
O'Mahony, M., Vertex Pharmaceuticals
Bunchatheeravate, P., Vertex Pharmaceuticals
Connelly, G., Vertex Pharmaceuticals
Successful manufacturing of pharmaceutical dosage forms require that the concentrations of formulation components are on target and consistent throughout product manufacturing. For continuous manufacturing of oral solid dosage forms the concentration of each formulation component is controlled by the dosing of loss-in-weight (LIW) feeders as well as mixing that occurs downstream of the feeders. Several authors have demonstrated that the residence time distribution of the system can be used to predict product concentrations given upstream disturbances for a direct compression line1 or a continuous blender2.

The current work looks to employ a similar methodology to predict the effect of concentration disturbances at the feeders within a dry granulation line which contains more unit operations that can impart more mixing. A case study showing the residence time distribution within the dry granulation line and the robust range of disturbances that can be accommodated will be presented. The system dynamics along with the response rate of the LIW feeders indicate that short-term fluctuations are low risk to the product. Strategies to ensure long term variation does not occur will be discussed.

References

  1. García‐Muñoz, S. , Butterbaugh, A. , Leavesley, I. , Manley, L. F., Slade, D. and Bermingham, S. (2018), A flowsheet model for the development of a continuous process for pharmaceutical tablets: An industrial perspective. AIChE J., 64: 511-525. doi:1002/aic.15967
  2. Sebastian Escotet-Espinoza, Sara Moghtadernejad, Sarang Oka, Zilong Wang, Yifan Wang, Andres Roman-Ospino, Elisabeth Schäfer, Philippe Cappuyns, Ivo Van Assche, Mauricio Futran, Fernando Muzzio, Marianthi Ierapetritou,Effect of material properties on the residence time distribution (RTD) characterization of powder blending unit operations. Part II of II: Application of models,Powder Technology,Volume 344,2019,Pages 525-544,ISSN 0032-5910,https://doi.org/10.1016/j.powtec.2018.12.051.