It would probably be harder with 2 puppies because the larger one doesn't have the proper
discipline to know what to back off yet. that being said i have a yorkie (7 months now) who loves to play with my parents dogs; adult 130 lb bull mastif and 90ish lb malimute. We always supervise them, but they have been trained to play "gentle". also make sure that everyone gets equal amounts of attention so there is no jelousy issues. examples: see below 