Mixing, blending, homogenizing…why does it have to be so darn confusing???

Mixing of dry powders is arguably the most challenging process in a pharmaceutical manufacturing operation. What looks to be simple on a bench scale, could end up being a nightmare in a larger production-size mixer. Unlike liquids or gases, powders do not tend to self-diffuse, and an active external force is required for them to mix. The flip side of this coin is segregation, whereby particles tend to group together by their size, and therefore undo the mixing process. The speed and extent of 'size segregation' can add another dimension to the mixing challenge, as well as reduce the efficiency of some other processes such as filtration or drying of the particles. It is important to know when particles are segregating versus when it is simply a question of inadequate mixing, which will determine your mixer selection criteria. Where a low-shear mixer may not suffice, a high-shear mixer may be required—but comes with its own set of challenges!

Depending upon what mixing action is required, there are 3 basic mechanisms of solids mixing:

1. Diffusive mixing: Diffusion of particles as would happen in a tumbling mixer/blender where individual particles are moved relative to the neighboring particles. Suitable for mixing of free flowing particles.

2. Convective mixing: the 3-dimensional motion imparted to groups of particles to move them from one place to another, as would happen in a Nauta-type mixer. A combination of diffusion and convection may also be seen in some types of mixers. Both convective and diffusive mixing are fairly gentle on the particles themselves and particle breakage can be managed.

3. Shear mixing: energy is imparted to particles in a shearing action to establish slip-planes, often with the intention of changing the shape of the particle as would be required in blending of toner particles (more on toner blending in a later blog).

Once the correct mixing action is determined, a mixer type must then be established. Solids mixers may be categorized as:

1. Batch versus continuous: batch mixers are more flexible and would be chosen for hard to mix powders that may require extended mixing durations, whereas continuous mixers may be more suited for powders that mix easily and segregate easily as well. There are several other pros and cons that would also need to be considered.

2. Horizontal versus vertical: the choice of one over the other often depends upon the layout of the plant. A vertical mixer usually stands taller but has a smaller footprint, compared to a horizontal mixer. The mixer loading and unloading mechanism is also impacted.

3. Speed: High versus low speed (or shear) mixers impact the particles very differently. The low shear mixer usually has tip speeds of less than 5 m/s and would be used when particle integrity is important, whereas the high speed mixers usually have tip speed in excess of 25 m/s and would be used where energy needs to be imparted to the individual particles.

Establishing a mixing criteria is absolutely critical to selecting the right mixer. Also, understanding some of the powder handling challenges such as segregation, balling and caking, and changes in particle characteristics under the influence of the energy being imparted, will help greatly in choosing the right mixer for your needs. When it comes to mixing, there are so many different powders and so many varieties of mixers, that there’s no one-size-fits-all. While many OEMs have in-house experts that can help, their advice often is slanted to the type of mixer they bring to market. It’s best to find an impartial 3rd party that can help you find what’s right for your mixing challenge.