It very much depends on the specific materials which is why it is a "let's not get into this and just say 'better safe than sorry'" situation but: Even if the powder is settled, it is going to almost immediately get kicked up and re-mixed once you start spraying. Probably don't test this for yourself for obvious reasons, but that is why a "fresh" can of spray paint will basically always work. It might not be even for the first few sprays but it rapidly becomes even.

Over simplifying (because molecular dynamics and shit) but think of it like a really crowded room. You basically can't sit down, let alone lie down, if it is crowded enough. And even if you try, someone will nudge you (or kick you) and you will get going.

As the pressure decreases, the settled powder is less likely to be disturbed and you are more likely to wake up from your nap wondering why nobody else is waiting for the new Star Wars with you. And that is why paint cans have the shaker and so forth.

So if your fire extinguisher has settled/compacted to the point that it is not viable? It is almost guaranteed to be because of a pressure leakage and that would be reflected on the gauge.

Now, there is probably some variant where this can happen regardless. But that would be a bad product anyway because these need to work even if nobody can ever be bothered to find the key to the glass box.