Pharmaceutical Powder Segregation

Powder Segregation

• 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.

Trajectory Segregation

• Larger particles have more kinetic energy and travel farther during mixing.
• This can lead to separation based on particle size.

Percolation Segregation

• 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.

Elutriation Segregation

• 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.

Minimizing Segregation

• 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.

Mixing Rates

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

Mixing Time and Content Standard Deviation

• 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.