This is in the wrong forum; it should really be in the MC21 for Mac forum. I'm not an admin, so I can't move it...
Anyway, I've got rather a lot of experience with this problem myself. The thread I started on this is many pages long and goes through a lot of changes.
The two biggest things that seemed to help for me were:
1. Disabling App Nap for MC21. You'll need to cut and paste this command into a terminal window:
defaults write com.jriver.MediaCenter21 NSAppSleepDisabled -bool YES
If you don't know how to do that, just skip it for now and move on to the next item.
2. Increase software buffering for your sound device in MC21:
Tools > Options > Audio > Audio Device > Device Settings > Buffering > Software > (select value here)
I recommend starting with 250 mS, but 500 mS was much better for me. I'm currently running with 750 mS and that has reduced the audio dropouts down to very few.
2.A. Just for completeness also check your hardware buffering. It's in the box right below software buffering. It should be set to "Hardware Default". Some versions of MC21 shipped with it set to "Maximum", which caused a lot of audio problems.
For reference, here's my original thread. It's way too long to read it all, but just in case you wan to see it...
http://yabb.jriver.com/interact/index.php?topic=97571.0Brian.