The Simulator is a different PLC model, so you should use different project files (one for each PLC even, not just one for each PLC model).
It would be like connecting to a 230 then switching to a 450 and back and forth. There are features in the 450 that do not exist in the 230. (e.g. PID). So if you re-use the same project file, that project file will lose those settings as you switch between the different models.
The Simulator does not support CTRIO locally, but the hardware does (for example).
However, you may have some "disconnected modules" in your Simulator project that you could "reconnect" in your hardware. Look in the System Configuration under Module Configuration and see if you have any that are "disconnected".