(16a) Toward Simulation-Based Design of Pharmaceutical Processes

Particle and fluid-particle simulations have been widely used to model a range of processes across many industries. This presentation will review application of simulations to common pharmaceutical processes including material transport and storage, blending, granulation, comminution, compaction, coating, and die filling. In many cases, simulations enable detailed analysis and flow visualization which provide insights into the effect of material properties and operating conditions promoting new designs and innovations and reducing inefficiencies and cutting costs associated with additional experimentation and scale-up studies.

Additionally, this presentation will review some computational models and techniques common to simulations involving particles. Recent advances in fluid-particle and particle models have significantly expanded the range of pharmaceutical systems and processes that can be described. Some of these advances include the modeling of particle mixes with wide variation in size, particle roughness, particle friction and particle cohesivity due to van der Waals or liquid bridging forces. Other model extensions include descriptions for particle aspericity that can also allow for particle breakage and flexibility. All of these complexities considerably affect the processing behavior of the particles. For example, surface moisture results in particle agglomeration, as is well known, but the particle aspect ratio determines the size and packing (solids volume fraction) of the agglomerates that are formed and the force required to convey or blend the particle mixture. And, when the solid volume fraction approaches the maximum packing density, the particle friction coefficient can be a more dominant factor than the liquid bridge force in determining the solid-phase shear stress.