A homogeneous blend is no guarantee of a homogeneous end product
In pharmaceutical manufacturing, an even distribution of active ingredients (APIs) throughout a powder blend is essential. Blending processes are therefore carefully designed and validated to achieve a uniform composition.
Yet an important risk often only arises after blending is complete. A blend that is fully homogeneous in the blender can still segregate during discharge, conveying and transfer to a tablet press or capsule filling machine.
This phenomenon is known as powder segregation. It can lead to variations in the concentration of active ingredients and thus to content uniformity problems in the end product.
Tip speed: not the whole story in blending
When assessing a blending process, tip speed is often considered: the peripheral speed at the outer edge of a mixer or blender. The formula is relatively simple:
v = π × D × N
Where:
- v = peripheral speed (m/s).
- D = blender diameter (m).
- N = rotational speed (revolutions per second).
With the same blender diameter and rotational speed, tip speed remains the same regardless of the fill level. That does not mean the blending behaviour stays the same.
The fill level affects how the powder moves in the blender. At a low fill level, a relatively thin moving powder layer forms. At a higher fill level, larger stagnant zones can develop, changing the blending motion.
That is why it is important not to look only at rotational speed or tip speed. Blending time, fill level, powder properties and particle size distribution also determine the final blending result.
Why segregation occurs during discharge
One of the most underestimated risks in powder processes arises at the transition from the blender to the next process step. Even when a blend is homogeneous in the blender, different particles can behave differently during discharge. Causes include:
- Differences in particle size: fine API particles and coarser excipients can move differently through a product stream, creating an uneven distribution during conveying or discharge.
- Differences in density: materials with different bulk densities can separate from each other during movement and free fall.
- Funnel flow: in funnel flow, mainly the material in the centre of a hopper moves downwards while material along the walls stays stationary for longer. This can cause segregation and variations in composition.
- Large drop heights: when powders fall freely over larger distances, particles can redistribute on landing according to their properties.
IBC blending: combining blending and transport
An interesting way to limit unnecessary product transfer is IBC blending (Intermediate Bulk Container blending). The blending process takes place in the IBC itself. After blending, the same container can be taken directly to the next process step.
This offers several advantages:
- Less manual product transfer.
- Fewer open process steps.
- Less dust formation.
- Lower risk of cross-contamination.
- The option of a closed connection to downstream equipment.
When the IBC is connected directly to a tablet press or capsule filling machine, a suitable docking solution or split butterfly valve can be used. Product transfer is then controlled and the system stays closed as far as possible.
For processes with potent active pharmaceutical ingredients (APIs), this is especially relevant. Limiting open transfers also helps protect operators.
Mass flow and short drop heights make the difference
Besides choosing a suitable blending system, the design of the outlet and hopper also deserves attention. In mass flow, the entire powder bed moves during discharge. This reduces the chance of stagnant zones and can help limit segregation.
It is also wise to keep free-fall heights as small as possible. The combination of suitable hopper geometry, controlled discharge and closed transfer can make an important contribution to process reliability.
The flow properties of the actual powder blend are decisive. A solution that works well for one blend does not automatically work for another.
Testing with the actual product
A blending process should not be assessed on theoretical calculations alone. It is the properties of the actual blend that determine how it behaves during blending, discharge and conveying.
It is therefore advisable to run practical tests at different fill levels. Check not only the homogeneity in the blender, but also the composition during and after discharge. Take samples at different positions, for example at the top, middle and bottom of the product stream, and include the discharge in the assessment. This shows whether the blend remains homogeneous during transfer.
From blender to end product: look at the complete process
At Hecht Technology we approach powder handling and containment as one integrated process. Selecting a suitable blender or mixer is not enough. The connections, discharge, transfer and feed to the next process step also determine the final process quality.
By aligning blending technology, closed conveying systems and containment solutions from the start, unnecessary process steps and risks can be reduced.
Conclusion
A homogeneous blend in the blender does not automatically mean a homogeneous end product. Segregation can occur during discharge, conveying and transfer, with possible consequences for the dose uniformity of pharmaceutical products. By paying attention to IBC blending, mass flow, short drop heights and closed transfer, this risk can be better controlled.