I'm going to go back to the loads and the firearm and leave the rest question alone.

Fliers can be caused by many things, one of those things is barrel heat.

If the "flyer" was usually the first shot or the last shot that the odds are that barrel heat may be a factor.

How fast were you shooting these groups and how hot was the barrel after #5.

I don't have a 221 Handgun, but I do have a 221 CZ 527 American.

I tested a lot of powders in this thing and some produced more barrel heat than others, IMR 4227 produced the most heat, it also produced the poorest groups.

2400 produced not only the least amount of heat it also produced the best groups.

Is there a correlation between heat and accuracy, prolly not, but I like the way 2400 allows me to shoot a whole bunch of rounds with one hole accuracy and zero flyers.

YMMV