I'm a little confused in why you are having trouble with the Arena game of MF. Not sure why you are using 50(!?) slots for an Arena team. Maybe I don't understand what your problem is, but I have done just fine with the 20 man Roster slot feature.
Ya, I have found that the program does not work well for Ironman Football substitution, but I think I have found a solution that makes Ironman Football possible with the 20 man roster sizes. Simply setup a 20 man roster with 3 QB's, 1 K, 10 WR's, 6 OL. You use the WR's in a variety of postions, mostly WR/DB's, but you can use them for FB/LB position, or have 2 or 3 of them as designated Defensive Specialists. I have used this setup and it works well for Ironman Football for the Arena game.