Among all dosage forms, orally administered pharmaceuticals are the most desirable due to their easy intake and practicality. Solid dosage forms, such as tablets and capsules, are thus a key staple in the manufacturing of pharmaceuticals. This involves many unit operations processing a broad variety of different materials all in powder form, each with a different set of characteristics and physical behaviour. Proper mixing is thus paramount to ensure that the product's final quality meets the desired standards. Therefore, powder blending is the foundation of every pharmaceutical manufacturing operation.
Despite it being a widespread operation, powder blending is a very complicated process. It involves many aspects, ranging from each material’s properties to the various operational parameters, making the blending quality almost impossible to predict without extensive testing. However, the scale of the process and the high value of the materials make extensive experimentation undesirable. This is particularly relevant for highly potent or hazardous ingredients, such as antibiotics. Virtual prototypes are thus a valuable asset to provide trends and insights for informed experimentation, reducing the amounts of trials necessary to design a process around a certain formulation.
We present a numerical case study where powder blenders of different designs and capacities are compared by using the Discrete Elements Method (DEM). In our study, we will focus on double-cone and V-shell blenders, together with the modular IBC designs, all with a capacity of several hundred litres. The blending profile of each is modelled for powders with a broad range of flow properties, from free-flowing materials prone to segregation to cohesive substances with a high tendency to agglomerate. Our study will explore two of the most important aspects of blending operations: scale-up and shell design transferability. Scale-up modelling will show how the mixing quality is affected when switching to a larger blender with the same shape, and how the change in scale impacts the mixing time. The in-silico transferability study will focus instead on predicting how the blending outcome is affected by changing the design of the blender in use, for instance when switching from a V-Shell to an IBC. These insights will be very useful to properly tailor the Design of Experiments during scale-up and blender design transferability by providing an informed choice of the process parameters range to test.
Learning Objectives:
Gather insights via virtual prototyping for informed experimentation in the context of powder blending.
Leverage numerical models to approach the problem of blending scale-up.
Understand which blender shell design and capacity are more suitable for powders with a certain flow behaviour.
