(M1330-06-35) Transformational Conical Mill Screen Design: A Paradigm Shift in Scalable Oral Solid Dosage Powder Size Reduction

Purpose: How CFD analysis and empirical DoE test data of recent screen design breakthroughs show an improvement in milling efficiency of APIs, excipients and OSD granulations without affecting validated particle size distributions (PSDs); including key considerations to ensure a predictable and successful scale-up transition from R&D development to OSD manufacturing can be attained for new product launches.

Methods: Research completed as a combination of numerical simulations through computation fluid dynamics (CFD) to anticipate mass flow through newly patented high efficiency screens; and supported by empirical data derived from a DoE test matrix with various pharmaceutical placebos/actives representing different material properties. DoE tests completed with a Quadro Comil and analyzed primarily with laser diffraction technology (Mastersizer 3000).

Results: Both CFD analysis and empirical DoE test results corroborate the improved mass flow (milling efficiency) of the new high efficiency screens regardless of the infeed materials properties and particle characteristics without negatively impacting validated particle size distributions (PSDs). Capacity throughput improvements averaged a 50% increase, with the added benefit of an average 10-15 degree C reduction in milling temperatures - thus safeguarding material properties of heat-sensitive powders.

Conclusion: There are a number of operational benefits to existing and/or future conical milling processes by the adoption of the high efficiency conical mill screens where capacities can be increased, milling temperatures reduced, without changing or shifting particle size distributions - thus ensuring validated processes and results remain unaffected.

References: 1. Patel R.P.; Baria A.H., Patel N.A. An Overview of Size Reduction Technologies in the Field of Pharmaceutical Manufacturing. Dep of Pharmaceutics, College of Pharma. Ed. and Res., India; Vol 2, Issue 4, pp.216-220 (2008)
2. Sunil S. Jambhekar. Bioavailability and Granule Properties. South University School of Pharmacy, Savannah, GA, USA ; Handbook of Pharmaceutical Technology, Chapter 19; Taylor and Francis, 2005
3. Elizabeth S. Fisher. Milling of Active Pharmaceutical Ingredients. Merck and Co., Inc., Rahway, New Jersey, U.S.A: Encyclopedia of Pharmaceutical Technology October 2006
4. Heng P.W.S. Energy-based Analysis of Cone Milling Process for the Comminution of Roller
Compacted Flakes. Int. J. of Pharmaceutics 462. 108-114 (2014)
5. Reynolds G.K. Modelling of Pharmaceutical Granule Size Reduction in a Conical Screen Mill; Chem.
Eng. Journal 164, 383-392 (2010)


Figure 1: Legacy vs High Efficiency Screen CFD Mass Pressure Comparison


Figure 2: Legacy vs High Efficiency Screen CFD Air Flow Comparison


Figure 3: Legacy vs High Efficiency Screen CFD Air Mass Comparison