The blending of different ingredients together in a uniform mixture is one of the most basic of pharmaceutical unit operations, but it can also be one of the most challenging to control. The terms ‘blending’ and ‘mixing’ are often used interchangeably, but technically, they are somewhat different. Blending in its simplest form is the combining of two or more materials to produce a homogeneous mixture. These materials may be any combination of particulates (solids blending) or particulate and liquid (liquid-solid blending). Blending is a relatively gentle process. Mixing is more closely associated with liquid-liquid, gas-liquid, and viscous materials.
Solid and powder dose products contain multiple ingredients. These may include an Active Pharmaceutical Ingredient (API) and excipients, such as, for example, fillers, binders, lubricants, glidants, flavoring agents, colorants and disintegrants. It would be ideal if all these different materials were of the same particle size and shape, but that is not the case. Mono-size particles are easily mixed provided they are free flowing. With multi-size different density and shape free flowing particles, segregation by size, density and rotational inertia are possible. Cohesive mixtures tend to be formed by fine particles. Fine (cohesive) particles with high surface forces (diameters <100um and very high forces with diameters <10um) may need agglomerate breakage requiring high power to obtain good blending. Smaller particles lead to a larger number of particles for a given sample mass. As the number of particles increase, the sample variance should go down. However with cohesive materials, the variance may actually increase due to aggregates. The characteristics of the powder can make all the difference in the success or failure of the blending process.
Blending Mechanisms
Diffusion — an expanded bed of free flowing material occurs with particles in random movements
Convection — when volumes or regions of the mix are moved en-masse to different areas
Shear — mixing occurs along slip planes between regions of particles
All mechanisms may exist in a single blender, but one or two may predominate. Cohesive powders are more likely to require shear (and convection) i.e. blades and ploughs are more appropriate than tumbling.
Blender Selection
Before selecting any blending system, it is necessary to understand the characteristics of the materials to be blended, how the material(s) is/are transported to and from the blender, and how the blender will be integrated into the plant.
Key considerations include:
- Material characteristics
- Loading and unloading requirements
- Easy product changeover
- Man-power availability
- Material lumping
- Single-floor or multi-floor operation
- Daily through-put requirements
- Process flow Specific industry regulations
- Dust control
- Safety
Blender Scale up Considerations
Because of the many different types of powders, scale-up is best done in a similar blender. Rotational speed is the second major factor in the scale-up of powder blending equipment. The degree of uniformity of a blend depends more strongly on the number of revolutions made by a blender than on the speed of the revolutions. As the equipment scales-up, the speed of the revolution decreases.
The rate, order and location of ingredient addition should be considered during development to be sure that the blending operation will yield suitable product at the production scale.
Blending Uniformity
The quality of blending is often determined by invasive thief sampling, followed by an off-line chemical analysis of the sampled material. The variance reduces in a logarithmic way towards the random value, but segregation may cause the curve to rise up again and poor blender selection, or operation may mean that the random value is never obtained.
Blender Type
There are a number of considerations for selecting the blender type. One of the first questions to ask is whether the process will be Batch or Continuous. In batch blending, the whole batch can be identified and is traceable to help with overall quality control. Batch operations are very versatile and one blender can be used for multipurpose operations including the blending several ingredients together. Continuous Blending includes metering of solids out at continuous and well defined rate. It requires precise powder control.
Batch Size
Don’t assume biggest is best! Some blender designs may not achieve a full homogeneous mix when the volume is large or the mixing time is extended.
Mixing Time
The shorter the mixing time to achieve a homogeneous mix, the lower the costs will be and there will be less product degradation with sensitive materials. Look for efficiency in blending operations with gentle actions.
Blender Designs
Rotating Shapes – Tumbling action that induces particles to roll and fall. Material is elevated beyond the angle of repose and it falls to the free surface. Rotating shape blenders demonstrate easy cleaning, emptying, low power consumption and moderate to low equipment wear.
Ribbon Blade – An agitator blends material in a trough. Ribbon blenders provide gentle blending with shear and impaction. They are not suitable for cohesive materials, and are difficult to clean. They are used mainly for the mixtures that require the of small amounts to larger components.
Orbiting Screw – Material is lifted up through the blender and spread out. They require moderate power consumption and are relatively easy to clean.
Principles of Tumble Blending
Normal tumble blending of free flowing materials provides a gentle mixing action. For materials that tend to lump or for high intensity blending, an internal agitator can be utilized. Critical to any blending operation is the quality of the blend, i.e., batch variations. Different applications have varying requirements for product uniformity.
V-shape Blenders are very popular in a wide variety of industries. They offer both short blending times and efficient blending. The blend is achieved by the constant, dividing and intermeshing particle movement provided by two connected cylinders. This precise mixing action results in blend variations of 1-2%.
The Twin Cone Blender design results in a high degree of particle mobility without the use of internal baffles. This type of blender has a low profile and requires less head-room than a V-blender. It is readily used in a wide variety of industries and applications and offers high efficiency with a blend variation of 1-2%.
The asymmetrical geometry of the Slant Cone Blender design offers a very fast blend time. High particle mobility, plus the intermeshing action of materials results in blend times up to 33 percent less than other blender designs. This configuration achieves more control and more a precise end product with blend variation as low as ½ percent.
Bin Blending involves dual action blending principles. The first blending action is produced by a wave as the material is tumbled. This wave (or shear plane) occurs in the top ¼ of the product load. The second blending action is produced by the cradle orientation. The Bin is held at an angle to position the horizontal center of gravity 20° from the tumbling centerline. This geometry places the Bin shell walls at cross flow producing angles to the blend axis, acting as baffles as the product is tumbled.
Summary
For any blending operation, it is important to understand the characteristics of the materials to be blended. Blender Selection should be based on material characteristics, blender capacity, and process performance requirements.
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