This is a very difficult question to answer. First, a muzzleloading rifle is not intended for shooting at 300 yards. But if this is just a hypothetical question, I will say this, the heavier the ball, the better it will resist wind effects. However, it must have sufficient velocity to carry it at the flattest trajectory possible. This raises the next problem and that is the fact that the more weight the ball has, the more chamber pressure it takes to push it to a desired velocity. There comes a point at which the breach of the rifle has to be big enough to handle the pressures. Let's say that you choose a .54 caliber rifle to buck the wind better than a .45 caliber ball. Then to get it to the target fast enough to minimize wind effects and to be able to hit the target with any reasonable probability, you could need to have a very heavy barrel such as is found on bench guns. It is a tangled mess when one wants to shoot with reasonable accuracy at what is considered extreme ranges for a muzzleloading rifle shooting a patched round ball.
So, what is the best caliber rifle for shooting at targets at 300 yards? In my opinion it would be a rifle with a caliber of somewhere between .50 and .58 with the ball pushed at the highest reasonably achieved velocity. Design a barrel around that and then design the rifle based on that barrel and you have it.
