Pharmaceutical Powder Segregation

Study Notes

Segregation is the opposite of mixing, where components separate.
This is important in pharmaceuticals, as an already mixed product can become unmixed if segregation occurs.
Variations in particle properties cause different behaviors when moved, leading to separation.
Particles with similar properties tend to group together, creating areas with higher concentrations of a specific component in the powder bed.
Segregation is more likely with vibration and higher flowability of the powder.

Smaller particles tend to fall through the gaps between larger particles, often settling at the bottom of the mix.
This happens when a powder bed is disturbed, such as during vibration or pouring.

Very small particles (dust) can be carried upward by air currents during mixing or discharge.
These particles may remain suspended until the mixing or discharge stops and settle on top of larger particles.

Choosing particles of similar sizes or controlling crystallization to reduce variability.
Using excipients with suitable densities can impact segregation.
Minimizing agitation, vibration or movement during and after mixing helps prevent further separation.
Performing various processes within the same equipment reduces movement.

Initially, the rate of mixing is faster than the rate of demixing.
Eventually, the rate of demixing becomes faster than mixing, creating equilibrium.

Extended mixing times can possibly impact the content standard deviation of a mix prone to segregation.
A mixing time leading to an acceptable product can result from optimizing conditions.