mr16ga,
I have found shooting dragons with anything less than a .54 caliber with a muzzleloader or .45 caliber in a rifle cartridge is probably a big mistake .
A good .45-70 load from a distance especially if using a heavier bullet like a 525-535gr. Postell would probably work, but as I said you'd better have some separation. A good buffalo cartridge should be the minimum on the list for effectiveness. There are many others who would argue only a Dangerous Game rifle with 20bore being the smallest, a .476 or .577 double would be more appropriate should be used. Penetration is the key, and the larger slower 20 bore, 10s, 8s and 4s might not be the ticket.
I definitely wouldn't shoot one with a pistol cartridge like a .45 Colt. It might just make them mad.
~Mako