segregation

Segregation is the tendency of a well-mixed powder to unmix itself during handling. Anyone who has eaten from a box of muesli knows it: the small oats sift to the bottom while the big nuts and fruit rise to the top, even though it was packed evenly. A pharmaceutical blend can do the same on its way from blender to tablet press, undoing the very uniformity it was mixed to achieve.

It happens because particles of different size, density or shape respond differently to motion and gravity. Common mechanisms include percolation, where small particles trickle down through gaps between larger ones during vibration or flow; trajectory segregation, where particles of different mass fly different distances when a stream falls into a hopper; and fluidization or dusting, where fines are lifted by escaping air.

The consequence is serious for medicines. If a potent low-dose drug separates from its excipients, some tablets receive too much active ingredient and others too little, causing the batch to fail content uniformity and posing a safety risk. Segregation is one of the main reasons a process that mixes perfectly can still produce non-uniform doses.

It is controlled by narrowing the particle size distribution so components match, by granulating to bind fine drug onto larger carrier particles, by adding ordered or interactive mixing where fine drug adheres to coarse carriers, and by minimising free fall, vibration and transfer steps that drive demixing.